| 1. |
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| 2. |
- Haferlach, Claudia, et al.
(författare)
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Proposals for standardized Protocols for cytogenetic analyses of acute leukemias, chronic lymphocytic leukemia, chronic myeloid leukemia, chronic myeloproliferative disorders, and myelodysplastic syndromes
- 2007
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 46:5, s. 494-499
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Tidskriftsartikel (refereegranskat)abstract
- The impact of cytogenetic characterization based on chromosome banding analyses and fluorescence in situ hybridization on clinical decision making has increased dramatically during recent years. Therefore, laboratory techniques have to be optimized to provide reliable results for optimal patient care. In addition, quick and correct results save time and money by preventing unnecessary additional diagnostics and suboptimal treatment approaches. It was our aim to present proposals for standardized protocols to improve the diagnosis, and hence the treatment outcome, of hematologic malignancies.
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| 3. |
- Hallor, Karolin H, et al.
(författare)
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Genomic profiling of chondrosarcoma: chromosomal patterns in central and peripheral tumors.
- 2009
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 15:8, s. 2685-2694
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Histologic grade is currently the best predictor of clinical course in chondrosarcoma patients. Grading suffers, however, from extensive interobserver variability and new objective markers are needed. Hence, we have investigated DNA copy numbers in chondrosarcomas with the purpose of identifying markers useful for prognosis and subclassification. EXPERIMENTAL DESIGN: The overall pattern of genomic imbalances was assessed in a series of 67 chondrosarcomas using array comparative genomic hybridization. Statistical analyses were applied to evaluate the significance of alterations detected in subgroups based on clinical data, morphology, grade, tumor size, and karyotypic features. Also, the global gene expression profiles were obtained in a subset of the tumors. RESULTS: Genomic imbalances, in most tumors affecting large regions of the genome, were found in 90% of the cases. Several apparently distinctive aberrations affecting conventional central and peripheral tumors, respectively, were identified. Although rare, recurrent amplifications were found at 8q24.21-q24.22 and 11q22.1-q22.3, and homozygous deletions of loci previously implicated in chondrosarcoma development affected the CDKN2A, EXT1, and EXT2 genes. The chromosomal imbalances in two distinct groups of predominantly near-haploid and near-triploid tumors, respectively, support the notion that polyploidization of an initially hyperhaploid/hypodiploid cell population is a common mechanism of chondrosarcoma progression. Increasing patient age as well as tumor grade were associated with adverse outcome, but no copy number imbalance affected metastasis development or tumor-associated death. CONCLUSION: Despite similarities in the overall genomic patterns, the present findings suggest that some regions are specifically altered in conventional central and peripheral tumors, respectively.
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| 4. |
- Heikkinen, Katri, et al.
(författare)
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RAD50 and NBS1 are breast cancer susceptibility genes associated with genomic instability
- 2006
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 27:8, s. 1593-1599
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Tidskriftsartikel (refereegranskat)abstract
- The Mre11 complex, composed of RAD50, NBS1 and MRE11, has an essential role in the maintenance of genomic integrity and preventing cells from malignancy. Here we report the association of three Mre11 complex mutations with hereditary breast cancer susceptibility, studied by using a case-control design with 317 consecutive, newly diagnosed Northern Finnish breast cancer patients and 1000 geographically matched healthy controls (P = 0.0004). RAD50 687delT displayed significantly elevated frequency in the studied patients (8 out of 317, OR 4.3, 95% CI 1.5-12.5, P = 0.008), which indicates that it is a relatively common low-penetrance risk allele in this cohort. Haplotype analysis and the screening of altogether 512 additional breast cancer cases from Sweden, Norway and Iceland suggest that RAD50 687delT is a Finnish founder mutation, not present in the other Nordic cohorts. The RAD50 IVS3-1G > A splicing mutation leading to translational frameshift was observed in one patient, and the NBS1 Leu150Phe missense mutation affecting a conserved residue in the functionally important BRCA1 carboxyterminal (BRCT) domain in two patients, both being absent from 1000 controls. Microsatellite marker analysis showed that loss of the wild-type allele was not involved in the tumorigenesis in any of the studied mutation carriers, but they all showed increased genomic instability assessed by cytogenetic analysis of peripheral blood T-lymphocytes (P = 0.006). In particular, the total number of chromosomal rearrangements was significantly increased (P = 0.002). These findings suggest an effect for RAD50 and NBS1 haploinsufficiency on genomic integrity and susceptibility to cancer.
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| 5. |
- Jee, Kowan Ja, et al.
(författare)
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Genomic profiles and CRTC1-MAML2 fusion distinguish different subtypes of mucoepidermoid carcinoma.
- 2013
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Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952. ; 26:2, s. 213-222
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Tidskriftsartikel (refereegranskat)abstract
- Mucoepidermoid carcinoma is the most common salivary gland malignancy, and includes a spectrum of lesions ranging from non-aggressive low-grade tumors to aggressive high-grade tumors. To further characterize this heterogeneous group of tumors we have performed a comprehensive analysis of copy number alterations and CRTC1-MAML2 fusion status in a series of 28 mucoepidermoid carcinomas. The CRTC1-MAML2 fusion was detected by RT-PCR or fluorescence in situ hybridization in 18 of 28 mucoepidermoid carcinomas (64%). All 15 low-grade tumors were fusion-positive whereas only 3 of 13 high-grade tumors were fusion-positive. High-resolution array-based comparative genomic hybridization revealed that fusion-positive tumors had significantly fewer copy number alterations/tumor compared with fusion-negative tumors (1.5 vs 9.5; P=0.002). Twelve of 18 fusion-positive tumors had normal genomic profiles whereas only 1 out of 10 fusion-negative tumors lacked copy number alterations. The profiles of fusion-positive and fusion-negative tumors were very similar to those of low- and high-grade tumors. Thus, low-grade mucoepidermoid carcinomas had significantly fewer copy number alterations/tumor compared with high-grade mucoepidermoid carcinomas (0.7 vs 8.6; P<0.0001). The most frequent copy number alterations detected were losses of 18q12.2-qter (including the tumor suppressor genes DCC, SMAD4, and GALR1), 9p21.3 (including the tumor suppressor genes CDKN2A/B), 6q22.1-q23.1, and 8pter-p12.1, and gains of 8q24.3 (including the oncogene MAFA), 11q12.3-q13.2, 3q26.1-q28, 19p13.2-p13.11, and 8q11.1-q12.2 (including the oncogenes LYN, MOS, and PLAG1). On the basis of these results we propose that mucoepidermoid carcinoma may be subdivided in (i) low-grade, fusion-positive mucoepidermoid carcinomas with no or few genomic imbalances and favorable prognosis, (ii) high-grade, fusion-positive mucoepidermoid carcinomas with multiple genomic imbalances and unfavorable prognosis, and (iii) a heterogeneous group of high-grade, fusion-negative adenocarcinomas with multiple genomic imbalances and unfavorable outcome. Taken together, our studies indicate that molecular genetic analysis can be a useful adjunct to histologic scoring of mucoepidermoid carcinoma and may lead to development of new clinical guidelines for management of these patients.Modern Pathology advance online publication, 28 September 2012; doi:10.1038/modpathol.2012.154.
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| 6. |
- Lindgren, David, et al.
(författare)
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Recurrent and multiple bladder tumors show conserved expression profiles.
- 2008
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 8:June 30
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Urothelial carcinomas originate from the epithelial cells of the inner lining of the bladder and may appear as single or as multiple synchronous tumors. Patients with urothelial carcinomas frequently show recurrences after treatment making follow-up necessary. The leading hypothesis explaining the origin of meta- and synchronous tumors assumes a monoclonal origin. However, the genetic relationship among consecutive tumors has been shown to be complex in as much as the genetic evolution does not adhere to the chronological appearance of the metachronous tumors. Consequently, genetically less evolved tumors may appear chronologically later than genetically related but more evolved tumors. METHODS: Forty-nine meta- or synchronous urothelial tumors from 22 patients were analyzed using expression profiling, conventional CGH, LOH, and mutation analyses. RESULTS: We show by CGH that partial chromosomal losses in the initial tumors may not be present in the recurring tumors, by LOH that different haplotypes may be lost and that detected regions of LOH may be smaller in recurring tumors, and that mutations present in the initial tumor may not be present in the recurring ones. In contrast we show that despite apparent genomic differences, the recurrent and multiple bladder tumors from the same patients display remarkably similar expression profiles. CONCLUSION: Our findings show that even though the vast majority of the analyzed meta- and synchronous tumors from the same patients are not likely to have originated directly from the preceding tumor they still show remarkably similar expressions profiles. The presented data suggests that an expression profile is established early in tumor development and that this profile is stable and maintained in recurring tumors.
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| 7. |
- Mandahl, Nils, et al.
(författare)
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Cytogenetic aberrations and their prognostic impact in chondrosarcoma
- 2002
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 33:2, s. 188-200
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Tidskriftsartikel (refereegranskat)abstract
- Chondrosarcoma is the second most common primary malignancy of bone. Cytogenetic data are available from close to 100 cases, including all subtypes of chondrosarcoma. Specific chromosomal rearrangements have been identified only in extraskeletal myxoid chondrosarcoma (EMC). Strong prognostic factors are largely missing, although size and, in particular, histologic tumor grade have been implicated. In the present study, we investigated the genomic aberrations in 59 chondrosarcomas (six grade 1, 24 grade 2, and 29 grade 3, including dedifferentiated tumors), excluding EMC, by chromosome banding analysis and DNA flow cytometry and correlated the findings with clinical outcome. Hyperhaploid to near-diploid karyotypes were found in half of the cases, and there was a good correlation between cytogenetics and flow cytometry data; discrepancies were seen primarily in cases with normal karyotypes and in those with -Y as the sole anomaly. Abnormal karyotypes, excluding those with -Y as the only change, were found in 36 cases. No recurrent structural aberration was found, but a nonrandom pattern of aberrations was seen. Total or partial gains and losses were the dominant karyotypic features. Genomic imbalances found in at least 10 cases included -1p36, -1p13-p22, -4, -5q13-q31, -6q22-qter, +7p13-pter, -9p22-pter, -10p, -10q24-qter, -11p13-pter, -11q25, +12q15-qter, -13q21-qter, -14q24-qter, -18p, -18q22-qter, +19, +20pter-q11, +21q, and -22q13. At the latest follow-up, 19 patients had experienced distant metastases, and the 5-year metastasis-free survival rate was 0.69. By univariate analysis, malignancy grade and loss of material from 6q, 10p, 11p or 11q, 13q, and 22q were associated with impaired metastasis-free survival. Only -13q was an independent prognostic factor for metastasis, regardless of tumor grade or size.
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| 8. |
- Menghi-Sartorio, Samantha, et al.
(författare)
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DNA copy number amplifications in sarcomas with homogeneously staining regions and double minutes
- 2001
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Ingår i: Cytometry. - : Wiley. - 0196-4763 .- 1097-0320. ; 46:2, s. 79-84
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Tidskriftsartikel (refereegranskat)abstract
- To identify DNA amplifications in sarcomas, comparative genomic hybridization was performed on 27 cases that were likely to display high-level DNA copy number gains. In all cases, chromosome banding analysis had revealed homogeneously staining regions or double minutes, i.e., cytogenetic signs of gene amplification. In most cases, gains predominated over losses. Low-level amplifications (ratio 1.3:1.5) were seen in 20 cases. High-level amplifications (ratio >1.5) exceeded the frequencies seen in published, unselected sarcomas of similar histotypes and were detected in 16 tumors: 4/4 osteosarcomas, 5/8 malignant fibrous histiocytomas, 3/7 leiomyosarcomas, 1/2 myosarcomas, 0/1 liposarcoma, 0/1 rhabdomyosarcoma, 1/1 pleomorphic sarcoma, 0/1 myxofibrosarcoma, 1/1 malignant mesenchymona, and 1/1 malignant schwannoma, with two to four chromosomal regions involved in nine tumors. Recurrent amplifications involved 1p33-p32, 5p15-p14, 7pter-p12, 7q21-qter, 8q21.3-qter, 11q22-q23, 16p13.2-p12, 19q12-q13.1, 20q11.2-qter, and 22q12-q13. Most of the recurrent gains/amplifications we detected have been reported in sarcomas previously. A novel gain/amplification was seen at 2q14.3-q21 in five cases of four sarcoma types. The disparate pattern of amplified sequences, the poor correspondence between the localization of low- and high-level amplifications, and the chromosomal position of homogeneously staining regions suggest the involvement of many genes in the amplifications and that the genes rarely maintain their native position in these tumors.
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| 9. |
- Niini, Tarja, et al.
(författare)
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Homozygous deletions of cadherin genes in chondrosarcoma-an array comparative genomic hybridization study
- 2012
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Ingår i: Cancer Genetics. - : Elsevier BV. - 2210-7762. ; 205:11, s. 588-593
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Tidskriftsartikel (refereegranskat)abstract
- Chondrosarcoma is a malignant bone tumor that is often resistant to chemotherapy and radiotherapy. We applied high resolution oligonucleotide array comparative genomic hybridization to 46 tumor specimens from 44 patients with chondrosarcoma and identified several genes with potential importance for the development of chondrosarcoma. Several homozygous deletions were detected. The tumor suppressor genes CDKN2A and MTAP were each homozygously deleted in four of the cases, and the RB1 gene was homozygously deleted in one. Two homozygous deletions of MTAP did not affect CDKN2A. Deletions were also found to affect genes of the cadherin family, including CDH4 and CDH7, each of which had a targeted homozygous loss in one case, and CDH19, which had a targeted homozygous loss in two cases. Loss of the EXT1 and EXT2 genes was uncommon; EXT1 was homozygously deleted in none and EXT2 in two of the cases, and large heterozygous losses including EXT1 and/or EXT2 were seen in three cases. Targeted gains and amplifications affected the MYC, E2F3, CDK6, PDGFRA, KIT, and PDGFD genes in one case each. The data indicate that chondrosarcomas develop through a combination of genomic imbalances that often affect the RB1 signaling pathway. The inactivation of cadherin genes may also be critical in the pathogenesis of the tumor.
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| 10. |
- Sarhadi, Virinder, et al.
(författare)
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Gut Microbiota and Host Gene Mutations in Colorectal Cancer Patients and Controls of Iranian and Finnish Origin
- 2020
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Ingår i: Anticancer Research. - : INT INST ANTICANCER RESEARCH. - 0250-7005 .- 1791-7530. ; 40:3, s. 1325-1334
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Gut microbiota plays an important role in colorectal cancer (CRC) and its composition in CRC patients can be influenced by ethnicity and tumour genomics. Herein, the aim was to study the possible associations of ethnicity and gene mutations with the gut microbiota in CRC patients.Materials and Methods: Bacterial composition in stool samples of 83 CRC patients and 60 controls from Iran and Finland was studied by 16S rRNA gene sequencing. The association of gut microbiota composition with CRC, host mutations in KRAS, NRAS and TP53, and ethnicity analysed.Results: Beta diversity analysis indicated significant differences between the Iranian and Finnish gut microbiota composition, in both controls and patients' groups. The Iranian controls had higher abundance of Prevotella and lower abundance of Bacteroides compared to the Finnish controls, while the Finnish patients had higher abundance of Clostridium compared to Iranian patients. Abundance of Ruminococcus was higher in patients compared to the controls. Higher abundances of Herbaspirillum, Catenibacterium and lower abundances of Barnesiella were associated with mutations in NRAS, TP53, and RAS respectively.Conclusion: A possible link of host gene mutations with gut bacterial composition is suggested.
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