| 1. |
- Heim, Sverre, et al.
(author)
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Cytogenetic nomenclature
- 2015. - 4th
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In: Cancer Cytogenetics : Chromosomal and Molecular Genetic Aberrations of Tumor Cells, - Chromosomal and Molecular Genetic Aberrations of Tumor Cells. - Chichester, UK : John Wiley & Sons, Ltd. - 9781118795538 - 9781118795569 ; , s. 19-25
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Book chapter (peer-reviewed)abstract
- This chapter elaborates on human chromosome nomenclature. It provides a brief summary of the most essential cytogenetic terminology related to the description of chromosome aberrations in neoplastic cells. The chapter outlines criteria for designation of regions and bands for chromosome nomenclature. Regions and bands are numbered consecutively from the centromere outward along each chromosome arm. This chapter outlines guidelines and conventions foy karyotypic nomenclature. It provides a detailed account on nomenclature of tumor cell populations. The introduction of various in situ hybridization technologies into the cytogenetic analysis of interphase and metaphase cells has led the International Standing Committee on Human Cytogenetic Nomenclature to propose an in situ hybridization (ish) nomenclature system that may be used to describe abnormalities at the molecular level by indicating, for example, the presence, absence, amplification, or separation of specific probe signals.
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| 2. |
- Heim, Sverre, et al.
(author)
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Nonrandom chromosome abnormalities in cancer : An overview
- 2015. - 4th
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In: Cancer Cytogenetics : Chromosomal and Molecular Genetic Aberrations of Tumor Cells - Chromosomal and Molecular Genetic Aberrations of Tumor Cells. - Chichester, UK : John Wiley & Sons, Ltd. - 9781118795538 - 9781118795569 ; , s. 26-41
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Book chapter (peer-reviewed)abstract
- This chapter discusses neoplastic karyotypes. It emphasizes the difference between primary and secondary changes and address the questions of why, how, when, and where chromosome abnormalities arise; compare numerical and structural aberrations in terms of how they contribute to tumor development; and also touch upon the issues of what causes cancer-associated chromosome abnormalities and whether they are necessary and/or sufficient to transform a normal cell into a cancer cell. It discusses some of the more principal differences between the cytogenetic and molecular genetic approaches to the study of acquired somatic cell mutations. Numerous specific chromosomal abnormalities have been detected in almost all tumor types that have been examined. This chapter explores when do chromosome aberrations arise and in which cells do chromosome aberrations arise. It also discusses whether acquired chromosome aberrations are sufficient for neoplastic proliferation. The chapter discusses the general effects of structural and numerical chromosome abnormalities.
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| 3. |
- Heim, Sverre, et al.
(author)
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Preface to the Fourth Edition
- 2015. - 4th
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In: Cancer Cytogenetics : Chromosomal and Molecular Genetic Aberrations of Tumor Cells - Chromosomal and Molecular Genetic Aberrations of Tumor Cells. - Chichester, UK : John Wiley & Sons, Ltd. - 9781118795538 - 9781118795569
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Book chapter (other academic/artistic)
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| 4. |
- Mertens, Fredrik, et al.
(author)
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Tumors of the skin
- 2015. - 4th
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In: Cancer Cytogenetics : Chromosomal and Molecular Genetic Aberrations of Tumor Cells - Chromosomal and Molecular Genetic Aberrations of Tumor Cells. - Chichester, UK : John Wiley & Sons, Ltd. - 9781118795538 - 9781118795569 ; , s. 555-565
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Book chapter (peer-reviewed)abstract
- Skin cancer is the most common malignancy in humans. Clonal chromosome abnormalities have been reported in approximately 100 basal cell epitheliomas (BCC). In contrast to BCC, which has no recognized precursor lesion, squamous cell carcinoma (SCC) of the skin is known to develop through histologic stages, the most important of which are actinic keratosis (squamous cell dysplasia) and carcinoma in situ (severe dysplasia). A wide range of clinically and pathologically different benign and malignant melanocytic tumors are recognized. Appendageal tumors are subdivided into more than 30 benign and malignant subtypes showing apocrine and eccrine differentiation or follicular and sebaceous differentiation. Merkel cell carcinomas have near-diploid karyotypes, often showing rearrangements of chromosome 1. Dermal cylindromas may show similar genetic features to adenoid cystic carcinomas with the occurrence of a t (6; 9) (q22-23; p23-24) leading to a MYB-NFIB fusion gene.
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| 5. |
- Mitelman, Felix, et al.
(author)
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How it all began : Cancer cytogenetics before sequencing
- 2015. - 4th
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In: Cancer Cytogenetics : Chromosomal and Molecular Genetic Aberrations of Tumor Cells - Chromosomal and Molecular Genetic Aberrations of Tumor Cells. - Chichester, UK : John Wiley & Sons, Ltd. - 9781118795538 - 9781118795569 ; , s. 1-10
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Book chapter (peer-reviewed)abstract
- According to Boveri's hypothesis, chromosome abnormalities were the cellular changes causing the transition from normal to malignant proliferation. Technical difficulties prevented reliable visualization of mammalian chromosomes, in both normal and neoplastic cells, throughout the entire first half of the 20th century. Nowell and Hungerford's discovery greatly stimulated interest in cancer cytogenetics in the early 1960s, but for several reasons, the Ph chromosome long remained an exceptional finding. The advent of molecular genetics in the 1980s and the development of a range of powerful molecular cytogenetic technologies, such as fluorescence in situ hybridization (FISH), multicolor FISH, comparative genomic hybridization (CGH), various array-based genotyping technologies, and DNA and RNA sequencing, have widened one's knowledge and understanding of the molecular mechanisms that are operative in neoplastic initiation and progression. In the 100 years since Boveri first postulated that chromosome change may initiate the carcinogenic process, cancer cytogenetics has come of age.
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| 6. |
- Adeyinka, Adewale, et al.
(author)
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Comparative cytogenetic and DNA flow cytometric analysis of 242 primary breast carcinomas
- 2003
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In: Cancer Genetics and Cytogenetics. - 0165-4608. ; 147:1, s. 62-67
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Journal article (peer-reviewed)abstract
- The cytogenetic and DNA flow cytometric findings in 242 breast carcinomas were compared. The combined use of both techniques improved the detection of abnormal cell populations from 65% by cytogenetic analysis alone and 59% by DNA flow cytometric analysis alone to 84%. Informative and comparable cytogenetic and flow cytometric data were obtained for 155 tumors. Among these 155 tumors, there was good concordance (64%) between the estimates of genomic changes by the two methods. Most discrepancies were among the DNA-diploid cases, where cytogenetic analysis detected small genomic changes. There were, however, also some exceptions in which large genomic changes detected by one method were missed by the other. Of the specific breast cancer-associated cytogenetic aberrations subjected to separate correlation analysis, polysomy for chromosome 20 was significantly associated with a high S-phase fraction, whereas loss of the long arm of chromosome 16 and/or the presence of a der(1;16) were significantly associated with a low S-phase fraction. Our data show that cytogenetic and DNA flow cytometric analyses of breast carcinomas give largely comparable results, and that combining data from both methods significantly improves the information obtained by either technique used alone on the genetic abnormalities in these tumors.
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| 7. |
- Andersen, Mette K., et al.
(author)
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Paediatric B-cell precursor acute lymphoblastic leukaemia with t(1;19)(q23;p13) : clinical and cytogenetic characteristics of 47 cases from the Nordic countries treated according to NOPHO protocols
- 2011
-
In: British Journal of Haematology. - Oxford : Wiley. - 0007-1048 .- 1365-2141. ; 155:2, s. 235-243
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Journal article (peer-reviewed)abstract
- The translocation t(1;19)(q23;p13)/der(19) t(1;19) is a risk stratifying aberration in childhood B-cell precursor acute lymphoblastic leukaemia (BCP ALL) in the Nordic countries. We have identified 47 children/adolescents with t(1;19)/der(19) t(1;19)-positive BCP ALL treated on two successive Nordic Society of Paediatric Haematology and Oncology (NOPHO) protocols between 1992 and 2007 and have reviewed the clinical and cytogenetic characteristics of these cases, comprising 1.8% of all cases. The translocation was balanced in 15 cases (32%) and unbalanced in 29 cases (62%). The most common additional chromosome abnormalities were del(9p), i(9q), del(6q), and del(13q). The median age was 7 years, the median white blood cell (WBC) count was 16 x 10(9)/l, and the female/male ratio was 1.2. The predicted event-free survival (EFS) at 5 and 10 years was 0.79, whereas the predicted overall survival (OS) at 5 and 10 years was 0.85 and 0.82, respectively. Nine patients had a bone marrow relapse after a median of 23 months; no patient had a central nervous system relapse. Additional cytogenetic abnormalities, age, gender, WBC count or whether the t(1;19) was balanced or unbalanced did not influence EFS or OS. Compared to cases with t(12,21) and high hyperdiploidy, EFS was similar, but overall survival was worse in patients with t(1;19)/der(19) t(1;19) (P = 0.004).
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| 8. |
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| 9. |
- Bardi, G, et al.
(author)
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Tumor karyotype predicts clinical outcome in colorectal cancer patients
- 2004
-
In: Journal of Clinical Oncology. - 1527-7755. ; 22:13, s. 2623-2634
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Journal article (peer-reviewed)abstract
- Purpose To investigate the prognostic value of the overall karyotypic features and specific chromosome aberrations in colorectal cancer (CRC). Patients and Methods Cytogenetic features of 150 primary CRCs investigated at the time of surgery were correlated with patient survival by univariate and multivariate analyses, using classical clinicopathologic parameters as covariates. Results In univariate analysis, in addition to tumor grade and clinical stage, structural aberrations as well as rearrangements of chromosomes 8 and 16 were significantly correlated with shorter overall survival. Karyotypic complexity, rearrangements of chromosomes 8 and 16, and loss of chromosome 4 were significantly correlated with shorter disease-free survival. In multivariate analysis, in addition to tumor grade, the type of chromosome aberrations (structural or numerical), ploidy, and loss of chromosome 18 came across as independent prognostic factors in the group of all patients. In the subset of patients with stage I and II carcinomas, none of the clinicopathologic variables could independently predict patient survival, whereas the presence of structural chromosomal aberrations was the only independent predictor of poor prognosis. In the subset of patients with stage III carcinomas, the presence of structural changes of chromosome 8 was a stronger independent predictor of prognosis than was tumor grade. Conclusion Cytogenetic tumor features are valuable predictors of prognosis in CRC patients. The tumor karyotype should therefore be taken into account in the clinical management of patients with this disease, especially for patients having cancers of the early or intermediate stages I, II, and III.
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| 10. |
- Brandal, Petter, et al.
(author)
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Detection of a t(1;22)(q23;q 12) translocation leading to an EWSR1-PBX1 fusion gene in a myoepithelioma
- 2008
-
In: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 47:7, s. 558-564
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Journal article (peer-reviewed)abstract
- Chromosome banding as well as molecular cytogenetic methods are of great help in the diagnosis of mesenchymal tumors. Myoepithelial neoplasms of soft tissue including myoepitheliomas, mixed tumors, and parachordomas are diagnoses that have been increasingly recognized the last few years. It is still debated which neoplasms should be included in these morphologically heterogeneous entities, and the boundaries between them are not clear-cut. The pathogenetic mechanisms behind myoepithelial tumors are unknown. Only five parachordomas and one mixed tumor have previously been karyotyped, and nothing is known about their molecular genetic characteristics. We present a mesenchymal tumor classified as a myoepithelioma that had a balanced translocation t(1;22)(q23;q12) as the sole karyotypic change. A novel EWSR1-PBX1 fusion gene consisting of exons 1-8 of the 5'-end of EWSR1 and exons 5-9 of the 3-end of PBX1 was shown to result from the translocation. Both genes are known to be targeted also by other neoplasia-specific translocations, PBX1 in acute lymphoblastic leukemia and EWSR1 in several solid tumors, most of which are malignant. Based on the structure of the novel fusion gene detected, its transforming mechanism is thought to be the same as for other fusion genes involving EWSR1 or PBX1.
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| 11. |
- Brandal, Petter, et al.
(author)
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t(19;22)(q13;q12) Translocation Leading to the Novel Fusion Gene EWSRI-ZNF444 in Soft Tissue Myoepithelial Carcinoma
- 2009
-
In: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 48:12, s. 1051-1056
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Journal article (peer-reviewed)abstract
- Myoepithelial neoplasms of soft tissue have only recently been acknowledged as a separate diagnostic entity. To know based on histological appearance whether these tumors are benign or malignant is often difficult, and their tumorigenic mechanisms remain poorly understood. We report a myoepithelial carcinoma with an aberrant near-diploid karyotype, 43 similar to 47,XX,add(1)(p34)x2,add(3)(q27)x2,del(12)(q22),+add(18)(p11)x2,del(22)(q 11),+r, found in cells cultured from a lung metastasis. The deletion in 22q led us to search by molecular cytogenetic means for possible EWSRI rearrangements, and eventually a novel chimeric gene consisting of the 5'-end of EWSRI (22q12) and the 3'-end of ZNF444 (19q13) was found. How the new fusion gene contributes to tumorigenesis is unknown, but the finding of an EWSRI rearrangement suggests that this, possibly even the EWSRI-ZNF444, is a defining pathogenetic feature of at least a subset of these tumors. (C) 2009 Wiley-Liss, Inc.
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| 12. |
- Bullerdiek, Jörn, et al.
(author)
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Tumors of endocrine glands
- 2015. - 4th
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In: Cancer Cytogenetics : Chromosomal and Molecular Genetic Aberrations of Tumor Cells - Chromosomal and Molecular Genetic Aberrations of Tumor Cells. - Chichester, UK : John Wiley & Sons, Ltd. - 9781118795538 - 9781118795569 ; , s. 497-514
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Book chapter (peer-reviewed)abstract
- Cytogenetic information is available on roughly 600 neoplasms originating from the thyroid, parathyroid, pituitary, and adrenal glands; from the thymus; and from the endocrine pancreas. Trisomy 7 is found in 30% of adenomas with clonal cytogenetic aberrations. In both the benign and malignant tumors, a combination of gains of or from chromosomes 5, 7, 12, 17, 19, and 20 was observed. Almost all pituitary tumors arise from the adenohypophysis and are benign adenomas; carcinomas are very rare. The clinical heterogeneity of Neuroblastoma (NB) is well reflected by its cytogenetic and genomic features. Clonal chromosome abnormalities were reported in adrenocortical adenomas. Chromosome banding studies have detected cytogenetic aberrations in adrenocortical carcinomas. Clonal chromosome abnormalities have been reported in several thymomas, usually as part of near-diploid karyotypes as well as in a few thymic carcinomas. The use of comparative genomic hybridization (CGH)-based techniques may improve thymoma subtyping.
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| 13. |
- Callen, David F, et al.
(author)
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New chromosomal rearrangement, t(12;22)(p13;q12), in acute nonlymphocytic leukemia
- 1991
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In: Cancer Genetics and Cytogenetics. - 0165-4608. ; 51:2, s. 255-258
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Journal article (peer-reviewed)abstract
- The karyotype 47,XX, + 8,t(12;22)(p13;q12) was found at diagnosis in two patients with acute nonlymphocytic leukemia (ANLL). The bone marrow morphology of both patients corresponded to the M4 subtype of the French-American-British (FAB) classification. The translocation t(12;22) has not previously been reported as the sole structural aberration in ANLL.
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| 14. |
-
Cancer cytogenetics : Chromosomal and Molecular Genetic Aberrations of Tumor Cells
- 2015. - 4th
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Editorial collection (peer-reviewed)abstract
- The first three editions of this acclaimed book presented a much-needed conceptual synthesis of this rapidly moving field. Now, Cancer Cytogenetics, Fourth Edition, offers a comprehensive, expanded, and up-to-date review of recent dramatic advances in this area, incorporating a vast amount of new data from the latest basic and clinical investigations. New contributors reflecting broader international authorship and even greater expertise. Greater emphasis throughout on the clinical importance and application of information about cytogenetic and molecular aberrations. Includes a complete coverage of chromosome aberrations in cancer based on an assessment of the 60,000 neoplasms cytogenetically investigated to date. Now produced in full color for enhanced clarity. Covers how molecular genetic data (PCR-based and sequencing information) are collated with the cytogenetic data where pertinent. Discusses how molecular cytogenetic data (based on studies using FISH, CGH, SNP, etc) are fused with karyotyping data to enable an as comprehensive understanding of cancer cytogenetics as is currently possible.
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| 15. |
- Elmula, Imad, et al.
(author)
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Chromosomal aberrations in benign and malignant Bilharzia-associated bladder lesions analyzed by comparative genomic hybridization.
- 2002
-
In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 2:5
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Journal article (peer-reviewed)abstract
- BACKGROUND: Bilharzia-associated bladder cancer (BAC) is a major health problem in countries where urinary schistosomiasis is endemic. Characterization of the genetic alterations in this cancer might enhance our understanding of the pathogenic mechanisms of the disease but, in contrast to nonbilharzia bladder cancer, BAC has rarely been the object of such scrutiny. In the present study, we aimed to characterize chromosomal imbalances in benign and malignant post-bilharzial lesions, and to determine whether their unique etiology yields a distinct cytogenetic profile as compared to chemically induced bladder tumors. METHODS: DNAs from 20 archival paraffin-embedded post-bilharzial bladder lesions (6 benign and 14 malignant) obtained from Sudanese patients (12 males and 8 females) with a history of urinary bilharziasis were investigated for chromosomal imbalances using comparative genomic hybridization (CGH). Subsequent FISH analysis with pericentromeric probes was performed on paraffin sections of the same cases to confirm the CGH results. RESULTS: Seven of the 20 lesions (6 carcinomas and one granuloma) showed chromosomal imbalances varying from 1 to 6 changes. The most common chromosomal imbalances detected were losses of 1p21-31, 8p21-pter, and 9p and gain of 19p material, seen in three cases each, including the benign lesion. CONCLUSION: Most of the detected imbalances have been repeatedly reported in non-bilharzial bladder carcinomas, suggesting that the cytogenetic profiles of chemical- and bilharzia-induced carcinomas are largely similar. However, loss of 9p seems to be more ubiquitous in BAC than in bladder cancer in industrialized countries.
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| 16. |
- Fadl-Elmula, Imad, et al.
(author)
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Characterization of chromosomal abnormalities in uroepithelial carcinomas by G-banding, spectral karyotyping and fish analysis
- 2001
-
In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 92:6, s. 824-831
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Journal article (peer-reviewed)abstract
- Chromosome analysis by G-banding, spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) was per formed on 24 short-term cultured transitional cell bladder carcinomas and 5 cell lines established from bladder carcinomas. Except for one tumor with an apparently normal chromosomal constitution, clonal chromosome abnormalities were detected in all examined cases by the combined approach. The application of SKY and FISH techniques improved the karyotypic descriptions, originally based on C-banding only, by identifying 32 additional numerical changes, by establishing the chromosomal origin of 27 markers and 2 ring chromosomes, by redefining 53 aberrations and by detecting 15 hidden chromosomal rearrangements. No recurrent translocation, however, was detected. The most prominent: karyotypic feature was thus the occurrence of deletions and losses of whole chromosome copies indicating the importance of tumor suppressor genes in transitional cell carcinoma pathogenesis. Invasive carcinomas were karyotypically more complex than were low grade superficial tumors. Specific leases of material from chromosome 9 and from chromosome arms I Ip and 8p, and gains of 8q and Iq seem to be early changes appearing in superficial tumors, whereas losses from 4p and 17p and the formation of an isochromosome for 5p were associated with more aggressive tumor phenotypes.
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| 17. |
- Fioretos, Thoas, et al.
(author)
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Chronic myeloid leukemia
- 2015. - 4
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In: Cancer Cytogenetics : Chromosomal and Molecular Genetic Aberrations of Tumor Cells - Chromosomal and Molecular Genetic Aberrations of Tumor Cells. - Chichester, UK : John Wiley & Sons, Ltd. - 9781118795538 - 9781118795569 ; , s. 153-174
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Book chapter (peer-reviewed)abstract
- Chronic myeloid leukemia (CML) is a clonal bone marrow (BM) disease characterized by neoplastic overproduction of, mainly, granulocytes. The treatment of CML has changed dramatically with the introduction of tyrosine kinase inhibitors (TKIs) targeting the product of the underlying cytogenetic and molecular lesion in CML. The Philadelphia chromosome was the first consistent neoplasia-associated chromosomal abnormality reported; its discovery was a milestone in cancer cytogenetics. Treatment of CML has changed dramatically over the last decades. The chfromosome t(9;22) (q34;q11) or its variant translocations (seen in 5-10%) are detected in the great majority of BM cells from patients with CML.The introduction of imatinib and other TKIs has dramatically improved the clinical outcome for CML patients, and today, the vast majority of patients receiving TKI treatment in chronic phase (CP) remain in complete hematologic and cytogenetic remission with low to undetectable BCR-ABL1 fusion transcripts.
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| 18. |
- Fioretos, Thoas, et al.
(author)
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Clinical impact of breakpoint position within M-bcr in chronic myeloid leukemia
- 1993
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In: Leukemia. - 1476-5551. ; 7:8, s. 1225-1231
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Journal article (peer-reviewed)abstract
- We have analyzed the M-bcr breakpoint position in 133 Philadelphia-positive chronic myeloid leukemia patients and correlated the findings with clinical, hematologic, and cytogenetic data. We also investigated the splicing pattern of the BCR-ABL mRNA in 30 patients, using reverse transcriptase PCR. No statistically significant differences were found between breakpoint position within M-bcr and clinical parameters at diagnosis, the karyotypic evolution pattern, or the leukemic phenotype during blast crisis. Furthermore, the breakpoint position within M-bcr did not correlate with the duration of chronic phase or survival time. When the splicing pattern of the BCR-ABL mRNA was compared with the results of the genomic breakpoint mapping, it was found that approximately 60% (8/14) of the patients with a 5' break expressed b2a2 fusion mRNA, whereas all patients (10/10) with a 3' break expressed b3a2 BCR-ABL mRNA.
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| 19. |
- Fioretos, Thoas, et al.
(author)
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Molecular analysis of Philadelphia-positive childhood chronic myeloid leukemia.
- 1992
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In: Leukemia. - 1476-5551. ; 6:7, s. 723-725
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Journal article (peer-reviewed)abstract
- The breakpoints in chromosome 22 were determined in five children with Philadelphia-positive chronic myeloid leukemia. All had rearrangements within the major breakpoint cluster region (M-bcr). Four patients had breakpoints in the 5' region of M-bcr (zones 1-3), whereas one had a rearrangement in the 3' region (zone 4). The patient with the 3' rearrangement was the only one to develop a lymphoid blast crisis; he also had a substantially longer survival (102 months) than the others (11-54 months).
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| 20. |
- Forestier, Erik, et al.
(author)
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Clinical and cytogenetic features of pediatric dic(9;20)(p13.2;q11.2)-positive B-cell precursor acute lymphoblastic leukemias : A nordic series of 24 cases and review of the literature
- 2008
-
In: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 47:2, s. 149-158
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Research review (peer-reviewed)abstract
- Although dic(9;20)(p13.2;q11.2) is a characteristic abnormality in childhood B-cell precursor acute lymphoblastic leukemias (BCP ALL), little is known about its clinical impact or the type and frequency of additional aberrations it may occur together with. We here review the clinical and cytogenetic features of a Nordic pediatric series of 24 patients with dic(9;20)-positive BCP ALL diagnosed 1996-2006, constituting 1.3% of the BCP ALL, as well as 47 childhood cases from the literature. Consistent immunophenotypic features of the Nordic cases included positivity for HLA-DR, CD10, CD19, CD20, and CD22 and negativity for T-cell and myeloid markers; no detailed immunophenotypes were reported for the previously published cases. In the entire cohort of 71 cases, the modal chromosome distribution was 45 (62%), 46 (21%), 47 (7%), 48 (4%), 49 (3%), 44 (1%), and 50 (1%). Additional changes were present in 63%, the most frequent of which were homozygous loss of CDKN2A (33%) and gains of chromosomes 21 (28%) and X (10%). The median patient age was 3 years, the female/male ratio was 2.0, the median white blood cell count was 24 x 10(9)/l, 11% had central nervous system involvement, and 5% had a mediastinal mass at diagnosis. Risk group stratification was nonstandard risk in 79%. The event-free survival and overall survival at 5 years for the 24 Nordic cases was 0.62 and 0.82, respectively. Thus, although relapses are quite common, postrelapse treatment of many patients is successful.
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| 21. |
- Forestier, Erik, et al.
(author)
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Cytogenetic patterns in ETV6/RUNX1-positive pediatric B-cell precursor acute lymphoblastic leukemia : A Nordic series of 245 cases and review of the literature
- 2007
-
In: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 46:5, s. 440-450
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Research review (peer-reviewed)abstract
- Between 1992 and 2004, 1,140 children (1 to <15 years) were diagnosed with B-cell precursor acute lymphoblastic leukemia (ALL) in the Nordic countries. Of these, 288 (25%) were positive for t(12;21)(p13;q22) [ETV6/RUNX1]. G-banding analyses were successful in 245 (85%); 43 (15%) were karyotypic failures. The modal chromosome numbers, incidence, types, and numbers of additional abnormalities, genomic imbalances, and chromosomal breakpoints in the 245 karyotypically informative cases, as well as in 152 previously reported cytogenetically characterized t(12;21)-positive ALLs in the same age group, were ascertained. The most common modal numbers among the 397 cases were 46 (67%), 47 (16%), 48 (6%), and 45 (5%). High-hyperdiploidy, triploidy, and tetraploidy were each found in 1%; none had less than 40 chromosomes. Secondary chromosomal abnormalities were identified by chromosome banding in 248 (62%) of the 397 ALLs. Of these, 172 (69%) displayed only unbalanced changes, 14 (6%) only balanced aberrations, and 26 (10%) harbored both unbalanced and balanced abnormalities; 36 (15%) were uninformative because of incomplete karyotypes. The numbers of secondary changes varied between 1 and 19, with a median of 2 additional aberrations per cytogenetically abnormal case. The most frequent genomic imbalances were deletions of 6q21-27 (18%), 8p11-23 (6%), 9p13-24 (7%), 11q23-25 (6%), 12p11-13 (27%), 13q14-34 (7%), loss of the X chromosome (8%), and gains of 10 (9%), 16 (6%), and 21 (29%); no frequent partial gains were noted. The chromosome bands most often involved in structural rearrangements were 3p21 (2%), 5q13 (2%), 6q12 (2%), 6q14 (2%), 6q16 (2%), 6q21 (10%), 6q23 (6%), 6q25 (3%), 9p13 (2%), 11q13 (2%), 11q23 (2%), 12p11 (6%), 12p12 (7%), 12p13 (25%), 21q10 (6%), and 21q22 (6%). Considering that the t(12;21) is known to arise in utero and that the postnatal latency period is protracted, additional mutations are most likely necessary for overt ALL. The frequently rearranged chromosome regions may harbor genes of importance for the transformation and/or progression of an initial preleukemic t(12;21)-positive clone.
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| 22. |
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| 23. |
- Gisselsson, David, et al.
(author)
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Cytogenetic methods
- 2015. - 4th
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In: Cancer Cytogenetics : Chromosomal and Molecular Genetic Aberrations of Tumor Cells - Chromosomal and Molecular Genetic Aberrations of Tumor Cells. - Chichester, UK : John Wiley & Sons, Ltd. - 9781118795538 - 9781118795569 ; , s. 11-18
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Book chapter (peer-reviewed)abstract
- This chapter outlines the methods currently employed in cancer cytogenetics, spanning from chromosome banding to array- and sequencing-based techniques. A correct sampling procedure is the basis for correct scientific and diagnostic conclusions. Chromosome preparation requires live cells, whereas in situ hybridization at least requires intact nuclei, and genome arrays as well as sequencing rely on DNA that has not been extensively degraded. Direct preparations or short-term cultures are therefore usually preferred for chromosome banding analysis. In situ hybridization techniques are based on the inherent organization of DNA into two antiparallel complementary strands. Genomic arrays are highly efficient tools for obtaining data on genomic imbalances present in a tumor sample. The advent of massive parallel/second-generation/ next-generation sequencing (NGS technology has radically transformed the field of cancer cytogenetics. More than 800 genomes of more than 25 cancer types have now been sequenced.
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| 24. |
- Gorunova, Ludmila, et al.
(author)
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Cytogenetic Analysis of 101 Giant Cell Tumors of Bone: Nonrandom Patterns of Telomeric Associations and Other Structural Aberrations
- 2009
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In: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 48:7, s. 583-602
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Journal article (peer-reviewed)abstract
- Giant cell tumor of bone (GCTB) is a benign but locally aggressive tumor with metastatic potential. We performed cytogenetic analysis on 10 1 GCTB from 92 patients. Karyotypes were obtained from 95 tumors, 47 of which had clonal aberrations. The majority of the cytogenetically abnormal GCTB had multiple, up to 28 per tumor, clones. Clonal telomeric associations (tas) and other structural and numerical changes were found in about 70, 60, and 30%, respectively, of clonally abnormal tumors. Forty-seven aberrations were recurrent, of which 35 are novel. The vast majority of the recurrent aberrations were tas, confirming the important role of telomeric fusions in the development of GCTB. The frequency of tas in GCTB cultures increased with passaging, suggesting a selective advantage of tas-positive cells in vitro. The termini most frequently involved in tas were 22p, 13p, 15p, 21p, 14p, 19q, 1q, 12p, 11p, and 20q. The frequency of tas (irrespective of their clonality) was significantly higher in tumors carrying clonal changes, indicating that tas are precursors of other types of aberrations. In line with this assumption, the chromosomes preferentially involved in tas in a given tumor were also the ones most often affected by other rearrangements. We did not find the previously reported amplicon in 20q11.1, assessed by fluorescence in situ hybridization in 10 tumors. Nor did we find any association between cytogenetic features and adverse clinical outcome. Thus, local recurrences probably depend more on the adequacy of surgical treatment than on the intrinsic biology of the tumors. (C) 2009 Wiley-Liss, Inc.
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| 25. |
- Harrison, Christine J., et al.
(author)
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Acute lymphoblastic leukemia
- 2015. - 4th
-
In: Cancer Cytogenetics : Chromosomal and Molecular Genetic Aberrations of Tumor Cells - Chromosomal and Molecular Genetic Aberrations of Tumor Cells. - Chichester, UK : John Wiley & Sons, Ltd. - 9781118795538 - 9781118795569 ; , s. 198-251
-
Book chapter (peer-reviewed)abstract
- Acute lymphoblastic leukemia (ALL) is classified as B-lineage ALL (B-ALL) and T-lineage ALL (T-ALL). The incidence of ALL is almost three times higher in white than black children. Among adults, ALL is more frequent in younger patients, with a median age of less than 30 years. The morphology-immunology-cytogenetics (MIC) subgroups are associated with nonrandom karyotypic abnormalities in a manner comparable to the specificity seen between chromosomal rearrangements and morphologic subgroups in acute myeloid leukemia. Low hyperdiploidy or hypodiploidy with 45 chromosomes and single numerical aberrations are increasingly being found as secondary changes associated with specific structural abnormalities. Cytogenetic analysis plays an integral part in the diagnosis of ALL. The abnormalities differ between B-ALL and T-ALL with different distributions between age groups. In association with these aspects, the diagnostic karyotype is an important prognostic variable. Children with Down syndrome (DS) have a greatly increased risk of developing acute leukemia, including ALL.
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| 26. |
- Heim, Sverre, et al.
(author)
-
A new specific chromosomal rearrangement, t(8;16) (p11;p13), in acute monocytic leukaemia
- 1987
-
In: British Journal of Haematology. - 0007-1048. ; 66:3, s. 323-326
-
Journal article (peer-reviewed)abstract
- The translocation t(8;16) (p11;p13) was found as the sole deviation from the normal karyotype in three patients with acute monocytic leukaemia. The bone marrow morphology was strikingly similar in the two cases where smears were available for re-evaluation: the leukaemic cells showed signs of differentiation, and active erythrophagocytosis was a particularly conspicuous feature. We suggest that t(8;16) (p11;p13) represents a new consistent abnormality in acute monocytic leukaemia, specifically associated with the differentiated subtype (M5b) and with pronounced phagocytic activity by the leukaemic monocytes.
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| 27. |
- Heim, Sverre, et al.
(author)
-
Acute myelomonocytic leukemia with inv(16)(p13q22) complicating Philadelphia chromosome positive chronic myeloid leukemia
- 1992
-
In: Cancer Genetics and Cytogenetics. - 0165-4608. ; 59:1, s. 35-38
-
Journal article (peer-reviewed)abstract
- The reciprocal translocation (9;22)(q34;q11) is highly characteristic of chronic myeloid leukemia (CML) and the pericentric inversion inv(16)(p13q22) is almost only found in acute nonlymphocytic leukemia of the myelomonocytic subtype (ANLL M4). Only twice before have an inv(16) and a t(9;22) been found in the same cells, and both times the patients seemed to have de novo ANLL M4. We describe the case of a 21-year-old man who in July 1986 presented with a clinically and hematologically classic chronic phase CML. Treatment with busulfan led to no improvement; instead in September 1986 he developed blast crisis with ANLL M4Eo morphology. He was now cytogenetically examined and the karyotype 45,X,-Y,t(9;22)(q34;q11),inv(16)(p13q22) was found. Southern blot analysis of the bone marrow DNA sampled at this time revealed a standard rearrangement in the 3' end of the M-bcr. Intensive cytostatic treatment caused cytopenia followed by complete hematologic, clinical, and cytogenetic reversal to chronic phase CML, so that in January 1987 the bone marrow karyotype was 46,XY,t(9;22)(q34;q11). Persistent splenomegaly was treated with splenectomy, and a chloroma of the skin was removed by irradiation. In March 1987 he received an allogeneic bone marrow transplant. Since then his only medical problem has been mild graft-versus-host disease; he is well and is working full time as a blacksmith.
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| 28. |
- Heim, Sverre, et al.
(author)
-
Bone marrow karyotypes in 94 children with acute leukemia
- 1990
-
In: European Journal of Haematology. - 1600-0609. ; 44:4, s. 227-233
-
Journal article (peer-reviewed)abstract
- During the last 10 years, we have cytogenetically analyzed at diagnosis bone marrow cells from a total of 94 children with acute leukemia. Of the 78 children with acute lymphatic leukemia (ALL), 53 (68%) had clonal acquired chromosome abnormalities; in the group with acute nonlymphatic leukemia (ANLL), the corresponding proportion was 13 out of 16 (81%). Among the cytogenetically abnormal ALL patients, the most numerous subset was the hyperdiploid cases with stemlines containing 51 or more chromosomes (26 of 53 abnormal cases; 49%). This is a clearly higher proportion than has been reported in large series from other centers. Deletions of 6q were present in 8 cases and rearrangements of 12p in 5. Of the 7 T-cell ALLs, 3 had translocations of the distal part of 7q, i.e., of the region where the beta T-cell receptor is encoded. Only 2 of 26 (8%) patients with leukemic stemlines with more than 50 chromosomes have relapsed; the remainder are still in first remission (mean observation time 42 months). This may be contrasted with 6 of 25 (24%) relapses among the cytogenetically normal (observation time 41 months), and 8 of 27 (30%) relapses among ALL patients with aberrations but with less than 51 chromosomes (observation time 26 months). Our results support the conclusion that the finding of a markedly hyperdiploid leukemia karyotype is indicative of good prognosis in ALL.
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| 29. |
- Heim, Sverre, et al.
(author)
-
High resolution banding analysis of the reciprocal translocation t(6;9) in acute nonlymphocytic leukemia
- 1986
-
In: Cancer Genetics and Cytogenetics. - 0165-4608. ; 22:3, s. 195-201
-
Journal article (peer-reviewed)abstract
- The cytogenetic, hematologic, and clinical characteristics of a 13-year-old girl with acquired t(6;9)(p23;q34) and dysmyelopoietic syndrome developing into acute myelomonocytic leukemia are described, bringing the total number of patients with t(6;9) and hematologic disease described in the literature up to 19. The diagnosis has been acute myeloid leukemia in the great majority of these patients; only four have had acute myelomonocytic leukemia. High resolution analysis at the 550 band stage localized the breakpoints in chromosomes #6 and #9 to p23 and 9q34.3, respectively. Previous investigations employing high resolution cytogenetics have mapped the typical 9q breakage site in chronic myeloid leukemia to 9q34.1. In situ hybridization studies have demonstrated that the cellular oncogene c-abl remains on the derivative 9q+ chromosome in t(6;9), whereas it is moved to the Ph marker in t(9;22). Thus, the combined data indicate that c-abl is located between 9q34.1 and 9q34.3, i.e., in subband 9q34.2 or its immediate vicinity.
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| 30. |
- Heim, Sverre, et al.
(author)
-
Molecular screening for new fusion genes in cancer
- 2008
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:6, s. 685-686
-
Journal article (other academic/artistic)abstract
- Gene fusions arising from translocations make an important contribution to the development of cancer. A new study uses high-throughput sequencing to characterize such fusions at an unprecedented level of resolution.
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| 31. |
- Heim, Sverre, et al.
(author)
-
New structural chromosomal rearrangements in congenital leukemia
- 1987
-
In: Leukemia. - 1476-5551. ; 1:1, s. 16-23
-
Journal article (peer-reviewed)abstract
- The karyotypic abnormalities and clinical data on three patients in whom acute leukemia was diagnosed within the first 6 months of life are presented. The four structural chromosomal rearrangements detected in the bone marrow from these patients, i.e., t(7;12)(q36;p13) and t(1;19)(q11;q11) in case 1, t(2;10;11;12)(q21q31;p13;q13;q24) in case 2, and t(11;19)(q23;p13) in case 3, have not previously been associated with congenital leukemia. Acquired chromosomal changes have until now been reported in only 31 leukemic infants in this age group. Of the total material, 18 patients had acute lymphoblastic leukemia and 16 had acute nonlymphocytic leukemia. The by far most frequently recorded cytogenetic aberration has been t(4q;11q), seen in 14 cases of lymphoblastic leukemia. Although t(4q;11q) has not been found in a single patient with acute nonlymphocytic leukemia, these leukemias have often had other rearrangements involving the same region of 11q. Hence, genetic material around 4q21 may be active in lymphocytic differentiation, whereas gene(s) in 11q23 may be important in the neoplastic process in a less cell-type specific manner and perhaps particularly vulnerable to neoplastic rearrangement in fetal life. The finding of four cases out of 34 with translocations between 11q23 and chromosome 19 indicates that this rearrangement might characterize a specific cytogenetic subgroup of leukemia in the very young.
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| 32. |
- Heim, Sverre, et al.
(author)
-
Reciprocal translocation (11;19)(q23;p13) in congenital acute lymphoblastic leukemia
- 1986
-
In: Cancer Genetics and Cytogenetics. - : Elsevier BV. - 0165-4608. ; 23:3, s. 239-244
-
Journal article (peer-reviewed)abstract
- The cytogenetic, clinical, and immunologic findings ina 4-month-old girl with acute lymphoblastic leukemia (ALL) are reported. The malignant lymphoblasts were characterized cytogenetically by the reciprocal translocation t(11;19)(q23;p13); immunologically by an immature pre-B-ALL phenotype. In spite of the high-risk nature of the leukemia, the patient attained complete remission relatively quickly and is still free of disease 3 years after diagnosis. Because the only two previously reported ALL patients with t(11;19) also seem to have responded well to therapy, this cytogenetic abnormality might turn out to be an indicator of favorable prognosis in ALL.
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| 33. |
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| 34. |
- Höglund, Mattias, et al.
(author)
-
Identification of cytogenetic subgroups and karyotypic pathways in transitional cell carcinoma
- 2001
-
In: Cancer Research. - 1538-7445. ; 61:22, s. 8241-8246
-
Journal article (peer-reviewed)abstract
- The clinical course in urinary bladder cancer is difficult or impossible to predict based on conventional disease parameters. It is a reasonable hypothesis that the genetic aberrations acquired by the tumor cells, being instrumental in bringing about the disease in the first place, may also hold the key to more reliable prognostication. However, though 200 transitional cell carcinomas (TCC), the most common bladder cancer in the Western world, with clonal chromosomal abnormalities have been reported, our knowledge about the karyotypic characteristics of these tumors remains insufficient. The aberration pattern is clearly nonrandom, but no completely specific primary or secondary karyotypic abnormality has been identified, and the chronological order in which the aberrations appear during disease progression is not well known. The high degree of karyotypic complexity in epithelial tumors like TCC is one reason why our picture of the sequential order of cytogenetic evolution is unclear. To overcome some of these difficulties we have used several statistical methods that allow analysis and interpretation of the relationship between cytogenetic aberrations in TCC. We show that there exists a temporal order with respect to the appearance of chromosomal imbalances and that this order is highly correlated with tumor stage and grade. Analyzing changes in the distribution of imbalances per tumor in G1, G2, and G3 tumors, we suggest that progression involves the acquisition of cytogenetically detectable and submicroscopic genetic changes at comparable frequencies. By means of computer simulations, we show that the imbalances -9, +7, and 1q+ appear earlier than expected from random events and that -6q, -5q, -18, +5p, -22p, and -15 appear later than expected. Using principal component analysis, we identify two cytogenetic pathways in TCC, one initiated by -9 and followed by -11p and 1q+, the other initiated by +7 and followed by 8p- and +8q. The -9 pathway was correlated with stage Ta-T2 tumors, whereas the +7 pathway was correlated with stage T1-T3 tumors, i.e., +7 tumors appeared to be more aggressive. Although these pathways are well separated at earlier stages, they later converge to contain a common set of imbalances.
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| 35. |
- Johansson, Bertil, et al.
(author)
-
Acute myeloid leukemia
- 2015. - 4th
-
In: Cancer Cytogenetics : Chromosomal and Molecular Genetic Aberrations of Tumor Cells - Chromosomal and Molecular Genetic Aberrations of Tumor Cells. - Chichester, UK : John Wiley & Sons, Ltd. - 9781118795538 - 9781118795569 ; , s. 62-125
-
Book chapter (peer-reviewed)abstract
- Acute leukemia is a worldwide disease with an incidence of approximately 4/100 000 per year; 70% of the cases are acute myeloid leukemia (AML). The salient pathologic feature of AML is the excessive accumulation of immature myeloid blasts in the bone marrow (BM). This maturation arrest, a characteristic of acute leukemias, prevents normal hematopoiesis and leads, directly or indirectly, to a lack of differentiated granulocytes, monocytes, thrombocytes, and erythrocytes. Chromosome banding analyses reveal acquired, clonal chromosomal abnormalities in the majority of AML cases, with the frequencies and types of aberrations to some extent being influenced by factors such as age, previous treatment/genotoxic exposure, gender, geographic/ethnic origin, and constitutional genetics. This chapter summarizes the cytogenetic, molecular genetic and clinical features of AML-associated numerical and structural abnormalities. It explains the characteristic karyotypic patterns in AML. Complex Karyotypic (CK), monosomal Karyotype (MK), normal Karyotype (NK) are the chromosomal abnormalities reported in AML.
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| 36. |
- JOHANSSON, BERTIL, et al.
(author)
-
Breakprone chromosome bands in fibroblasts from patients with non‐Hodgkin's lymphoma do not coincide with bands involved in primary rearrangements in non‐Hodgkin's lymphomas
- 1988
-
In: Hereditas. - : Springer Science and Business Media LLC. - 0018-0661. ; 109:1, s. 131-137
-
Journal article (peer-reviewed)abstract
- The distribution of breakpoints in structural chromosome aberrations (chromatid and chromosome gaps, breaks, and exchanges) was studied in skin fibroblasts from 35 untreated patients with non‐Hodgkin's lymphoma (NHL) and 39 controls. A total of 227 aberrations in the NHL group and 260 in the control group could be assigned to specific chromosome bands. The distribution of breakpoints was nonrandom in both groups (p<0.001), with excessive breakage in 17 bands among the NHL patients and in 21 among the controls. Two of the hot spots in the NHL group (6q21,14q24) and three in the control group (2q33,6q21, 6q25) coincided with the 60 chromosome bands that are targets for primary chromosome abnormalities in NHL. We conclude that the chromosome bands involved in primary structural abnormalities in lymphoma cells are not constitutionally breakprone in NHL patients.
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| 37. |
- JOHANSSON, BERTIL, et al.
(author)
-
Normal frequency of structural chromosome aberrations in fibroblasts from patients with non‐Hodgkin's lymphoma
- 1988
-
In: Hereditas. - : Springer Science and Business Media LLC. - 0018-0661. ; 109:2, s. 277-280
-
Journal article (peer-reviewed)abstract
- The incidence of chromosome aberrations, i.e., chromatid and chromosome gaps, breaks, and exchanges, was studied in cultured skin fibroblasts from 25 untreated patients with non‐Hodgkin's lymphoma (NHL) and 26 controls. The mean frequencies of aberrant cells, and gap, break, and gap+break events per 100 metaphases were 4.2, 1.9, 2.8, and 4.7 in the NHL group, and 5.1, 2.6, 3.2, and 5.8 in the control group. None of these parameters differed significantly between the groups, indicating that constitutional chromosomal instability is not related to the development of NHL. In the total material there was a significant (P<0.05) increase with age in the number of aberrant cells.
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| 38. |
- Johansson, Bertil, et al.
(author)
-
Remarkably long survival of a patient with Ph1-positive chronic myeloid leukemia and 5' bcr rearrangement
- 1990
-
In: Leukemia. - 1476-5551. ; 4:6, s. 448-449
-
Journal article (peer-reviewed)abstract
- Chronic myeloid leukemia (CML) was diagnosed in a 19-year-old man in 1961, and the disease remained in chronic phase, with occasional exacerbations, for 27 years. In 1976, when the first cytogenetic analysis was performed, t(9;22)(q34;q11) was found as the sole abnormality in all mitoses. During accelerated phase in 1988, a second cytogenetic investigation showed the karyotype 45,XY,t(9;22)(q34;q11),-15,-17,+der(15) t(15;17)(p13;q11). Molecular analysis revealed a rearrangement in the 5' end of the major breakpoint cluster region (M-bcr). With the case presented here, sublocalization of the bcr breakpoint has now been undertaken in altogether five CML patients with extremely long survival. It is noteworthy that in all these cases the chromosome 22 breakpoint was located in the 5' region of the M-bcr.
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| 39. |
- Johansson, Bertil, et al.
(author)
-
t(3;21)(q26;q22) with AML1 rearrangement in a de novo childhood acute monoblastic leukaemia
- 1996
-
In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 92:2, s. 429-431
-
Journal article (peer-reviewed)abstract
- t(3;21)(q26;q22) is a recurrent chromosomal abnormality in Philadelphia-positive chronic myeloid leukaemia in blast crisis and in treatment-related myelodysplastic syndrome and acute myeloid leukaemia. The molecular consequences of the t(3;21) are presently being unravelled; various transcripts between the AML1 gene in 21q22 and several unrelated genes, i.e. EAP, EVI1 and MDS1, in 3q26 are generated, resulting in the formation of a chimaeric transcription factor. The t(3;21) has only rarely been described in de novo leukaemias and never before in an acute leukaemia in a child. We here present the clinical, cytogenetic and molecular genetic findings in a boy with a de novo acute monoblastic leukaemia with t(3;21)(q26;q22) and AML1 rearrangement.
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| 40. |
- Karrman, Kristina, et al.
(author)
-
Clinical and cytogenetic features of a population-based consecutive series of 285 pediatric T-cell acute lymphoblastic leukemias: rare T-cell receptor gene rearrangements are associated with poor outcome.
- 2009
-
In: Genes, chromosomes & cancer. - : Wiley. - 1098-2264 .- 1045-2257. ; 48:9, s. 795-805
-
Journal article (peer-reviewed)abstract
- Clinical characteristics and cytogenetic aberrations were ascertained and reviewed in a population-based consecutive series of 285 pediatric T-cell acute lymphoblastic leukemias (T-ALLs) diagnosed between 1992 and 2006 in the Nordic countries. Informative karyotypic results were obtained in 249 (87%) cases, of which 119 (48%) were cytogenetically abnormal. Most (62%) of the aberrant T-ALLs were pseudodiploid. Structural changes were more common than numerical ones; 86% displayed at least one structural abnormality and 41% at least one numerical anomaly. The most frequent abnormalities were T-cell receptor (TCR) gene rearrangements (20%) [TCR;11p13 (10%), TCR;10q24 (3%), TCR;other (8%)], del(9p) (17%), +8 (14%), del(6q) (12%), and 11q23 rearrangements (6%). The TCR;other group comprised the rare rearrangements t(X;14)(p11;q11), t(X;7)(q22;q34), t(1;14)(p32;q11), ins(14;5)(q11;q?q?), inv(7)(p15q34), t(8;14)(q24;q11), t(7;11)(q34;p15), and t(12;14)(p13;q11). The clinical characteristics of this Nordic patient cohort agreed well with previous larger series, with a median age of 9.0 years, male predominance (male/female ratio 3.1), median white blood cell (WBC) count of 66.5 x 10(9)/l, and a high incidence of mediastinal mass and central nervous system involvement (59% and 9.5%, respectively). These features did not differ significantly among the various genetic subgroups. 5-year event-free survival (EFS) and overall survival for all patients were 0.61 (+/-0.03) and 0.67 (+/-0.03), respectively. In a multivariate analysis, two factors affected negatively the EFS, namely a WBC count of > or =200 x 10(9)/l (P < 0.001) and the presence of rare TCR rearrangements (P = 0.001). In conclusion, in this large series of childhood T-ALLs from the Nordic countries, the cytogenetic findings were not associated with risk of therapy failure with the exception of the TCR;other group. However, further prospective and collaborative investigations of this genetically heterogeneous entity are needed to confirm these results.
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| 41. |
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| 42. |
- KRISTOFFERSSON, ULF, et al.
(author)
-
CYTOGENETIC STUDIES IN HODGKIN'S DISEASE
- 1987
-
In: Acta Pathologica Microbiologica Scandinavica. Section A. Pathology. - 0108-0164. ; 95 A:1-6, s. 289-295
-
Journal article (peer-reviewed)abstract
- Cytogenetic analysis was attempted in 20 patients with Hodgkin's disease. No mitoses were found in 2 cases, normal metaphases in 7, and normal metaphases with nonclonal aberrations in 7. Of the 4 cases with clonal aberrations, one had +16 as the sole change, whereas the remaining tumors had multiple numerical and structural changes.
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| 43. |
- KRISTOFFERSSON, ULF, et al.
(author)
-
Cytogenetic studies in non‐Hodgkin lymphomas ‐ Results from surgical biopsies
- 1986
-
In: Hereditas. - : Springer Science and Business Media LLC. - 0018-0661. ; 104:1, s. 1-13
-
Journal article (peer-reviewed)abstract
- Cytogenetic analysis using Giemsa banding technique was successful in 30 of the 49 adult patients with nonHodgkin lymphomas investigated. The results are correlated with previous findings in 48 non‐Hodgkin lymphoma patients studied by means of fine needle aspiration in our laboratory. As 8 patients were included in both series, the total number successfully investigated was 70. The success rate with both sampling techniques was equivalent, and both methods also seemed to give qualitatively similar information about chromosome pattern. However, cells with a normal diploid karyotype were more frequent in the surgical biopsies. In the total material, normal karyotypes only were found in 10 patients. In two patients the aberrations were too complex to allow evaluation. The chromosome variation among the remaining 58 cases was distinctly nonrandom. Chromosomes 3, 7, 12, and 18 were preferentially gained, whereas chromosomes 1, 6, and 14 were most often involved in structural rearrangements. A 14q+ marker chromosome was the single most frequent abnormality; originating through t(14; 18) (q32; q21) in 10 of 23 cases. The second most common structural aberration was a deletion of the long arm of chromosome 6 with breakpoints at bands q15 and q21 (12 cases). At least one of the two most common numerical and/or structural changes, +7, +12, 14q+, and 6q‐, were present in 39 of the 58 patients with aberrations (67%). Longitudinal studies demonstrated karyotypic evolution during the course of the disease in five of six patients. Simultaneous samples from different tumor sites were studied in 10 patients. The findings in 9 cases suggested a monoclonal origin; in one case totally unrelated karyotypes were found in two different lymph nodes at third relapse, suggesting a multifocal origin.
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| 44. |
- Kristoffersson, Ulf, et al.
(author)
-
Deletion of 14q in non‐Hodgkin's lymphoma
- 1990
-
In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 44:4, s. 261-264
-
Journal article (peer-reviewed)abstract
- Abstract: 6 patients with non‐Hodgkin's lymphoma [3 with small cell lymphocytic lymphoma of B‐cell type (SL), and 1 each with follicular centroblastic/centrocytic, centroblastic, and immunoblastic lymphoma] and with the acquired cytogenetic abnormalities del(14) (q22) or del(14) (q24) are described. An evaluation of these 6 cases and 41 other lymphatic neoplasms with 14q deletion known from the literature revealed that 37 had a breakpoint in bands q22 to q24. The deletions occur significantly more often in lymphomas of SL morphology and in the leukemic counterpart, chronic lymphocytic leukemia, than in other types of lymphatic malignancies (p< 0.001).
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| 45. |
|
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| 46. |
- KRISTOFFERSSON, ULF, et al.
(author)
-
No abnormal C‐band polymorphism in lung cancer patients
- 1989
-
In: Hereditas. - : Springer Science and Business Media LLC. - 0018-0661. ; 110:3, s. 201-202
-
Journal article (peer-reviewed)abstract
- The C‐band heterochromatin polymorphism of chromosomes 1, 9, and 16 was studied in lymphocytes from 52 lung cancer patients and 183 control persons. No significant differences between the controls and patients were found regarding heterochromatin block size, the frequency of partial and total inversions, or the symmetry/asymmetry pattern.
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| 47. |
- Kristoffersson, Ulf, et al.
(author)
-
Prognostic implication of cytogenetic findings in 106 patients with non-Hodgkin lymphoma
- 1987
-
In: Cancer Genetics and Cytogenetics. - : Elsevier BV. - 0165-4608. ; 25:1, s. 55-64
-
Journal article (peer-reviewed)abstract
- The cytogenetic findings in samples from 106 patients with non-Hodgkin lymphomas (NHL), histopathologically classified according to the Kiel classification, have been correlated with survival time. Clonal chromosomal abnormalities were found in 60 patients, and only normal karyotypes in ten. The chromosome analysis of the remaining samples failed. The failures did not differ in survival compared with the cytogenetically successful cases, indicating that this group is not a prognostic entity within NHL. The cytogenetic findings were classified in six ways in order to evaluate the prognostic value of the cytogenetic pattern. Multivariate analysis demonstrated that presence of clonal chromosome abnormalities and the number of aberrations both were important prognostic factors independent of histopathology, whereas, the modal chromosome number, presence of translocations, or unidentified marker chromosomes were not. Some characteristic chromosome abnormalities were correlated with survival time: Patients with a 1p+ marker or +7 had a significantly shorter survival time than patients with normal karyotypes only (NN). Patients with +3, +12, 6q-, i(17q), and t(14;18)(q32;q21) did not differ significantly from the NN group.
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| 48. |
- KRISTOFFERSSON, ULF, et al.
(author)
-
RELATIONSHIP BETWEEN CYTOGENETIC FINDINGS AND HISTOPATHOLOGY IN NON‐HODGKIN LYMPHOMA
- 1987
-
In: Acta Pathologica Microbiologica Scandinavica. Section A. Pathology. - 0108-0164. ; 95 A:1-6, s. 1-5
-
Journal article (peer-reviewed)abstract
- The cytogenetic findings in 70 patients with non‐Hodgkin lymphoma have been correlated with tumor histopathology according to the Kiel classification. Certain chromosome aberrations displayed a nonrandom association with the grade of malignancy: 4 lymphomas out of 6 with 1p+, 5 out of 7 with del(6)(q15), 7 out of 11 with 14q+, and 5 out of 8 with +18 belonged to the high grade malignancy group, whereas 9 lymphomas out of 10 with t(14;18) were low grade malignant. Two aberration types were closely associated with specific histopathologic subtypes: t(14; 18) occurred in 7 cases out of 10 in centroblastic/ centrocytic (cb/cc) follicular lymphomas, and 5 cases out of 6 with i(17q) were cb or cb/cc. Although less striking, there was a tendency for del(6)(q15) to occur in cb or cb/cc lymphomas (4 cases out of 7), in contrast to only 1 case out of 5 with the more distal deletion del(6)(q21).
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| 49. |
- Kristoffersson, Ulf, et al.
(author)
-
Trisomy 5 and t(5;14)(q11;q32) as the sole abnormalities in two different clones from a centroblastic non-Hodgkin's lymphoma
- 1988
-
In: Cancer Genetics and Cytogenetics. - : Elsevier BV. - 0165-4608. ; 36:2, s. 173-176
-
Journal article (peer-reviewed)abstract
- A 62-year-old previously healthy woman presented with a centroblastic non-Hodgkin's lymphoma in the thyroid. Chromosome analysis revealed two unrelated clones, 47,XX,+5 and 46,XX,-14,+der(14)t(5;14)(q11;q32). The two clones may reflect a polyclonal origin, or they may be the descendants of the same neoplastically rearranged cell. In the latter case, the clonal aberrations are either secondary to an event detectable only at the molecular level, or one of them is a primary cytogenetic event while the other arose through clonal evolution with loss of the primary aberration. The best candidate for the primary change would be trisomy 5. Trisomy 5 has previously been associated with lymphomas with diffuse, large, noncleaved morphology, a group within the Working Formulation largely equivalent to centroblastic lymphomas in the Kiel classification. Our findings thus support the notion that trisomy 5 may be associated with centroblastic/diffuse, large, noncleaved lymphomas.
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| 50. |
- Lundin, Catarina, et al.
(author)
-
Clinical and genetic features of pediatric acute lymphoblastic leukemia in Down syndrome in the Nordic countries
- 2014
-
In: Journal of Hematology & Oncology. - : Springer Science and Business Media LLC. - 1756-8722. ; 7, s. 32-
-
Journal article (peer-reviewed)abstract
- Background: Children with Down syndrome (DS) have an increased risk for acute lymphoblastic leukemia (ALL). Although previous studies have shown that DS-ALL differs clinically and genetically from non-DS-ALL, much remains to be elucidated as regards genetic and prognostic factors in DS-ALL. Methods: To address clinical and genetic differences between DS-ALL and non-DS-ALL and to identify prognostic factors in DS-ALL, we ascertained and reviewed all 128 pediatric DS-ALL diagnosed in the Nordic countries between 1981 and 2010. Their clinical and genetic features were compared with those of the 4,647 B-cell precursor (BCP) ALL cases diagnosed during the same time period. Results: All 128 DS-ALL were BCP ALL, comprising 2.7% of all such cases. The 5-year event-free survival (EFS) and overall survival (OS) were significantly (P = 0.026 and P = 0.003, respectively) worse for DS-ALL patients with white blood cell counts >= 50 x 10(9)/l. The age distributions varied between the DS and non-DS cases, with age peaks at 2 and 3 years, respectively; none of the DS patients had infant ALL (P = 0.029). The platelet counts were lower in the DS-ALL group (P = 0.005). Abnormal karyotypes were more common in non-DS-ALL (P < 0.0001), and there was a significant difference in the modal number distribution, with only 2% high hyperdiploid DS-ALL cases (P < 0.0001). The 5-year EFS and 5-year OS were significantly worse for DS-ALL (0.574 and 0.691, respectively) compared with non-DS-ALL (0.783 and 0.894, respectively) in the NOPHO ALL-1992/2000 protocols (P < 0.001). Conclusions: The present study adds further support for genetic and clinical differences between DS-ALL and non-DS-ALL.
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