| 1. |
- Bartuma, Hammurabi, et al.
(författare)
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Cytogenetic and molecular cytogenetic findings in lipoblastoma.
- 2008
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Ingår i: Cancer Genetics and Cytogenetics. - : Elsevier BV. - 0165-4608. ; 183:1, s. 60-63
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Tidskriftsartikel (refereegranskat)abstract
- Lipoblastoma is a rare benign tumor that arises from embryonic adipose tissue and usually occurs in young children. Here, we present a review of available cytogenetic data and the karyotypes of 10 new cases of lipoblastoma, of which 7 could be studied further by fluorescence in situ hybridization (FISH) with regard to the involvement of the PLAG1 gene. All seven tumors with clonal aberrations harbored breakpoints in 8q11 approximately q13, in agreement with literature data. Including previously published cases, 33/40 (82%) lipoblastomas had rearrangement of the 8q11 approximately q13 region. These rearrangements target the PLAG1 gene, which becomes upregulated through promoter swapping. FISH revealed that five of seven cases in our series had a rearrangement of the PLAG1 gene. Occasionally, there can be difficulties in distinguishing a lipoblastoma from a conventional lipoma or a myxoid liposarcoma. As 8q11 approximately q13 rearrangements have been reported in only 3% of conventional lipomas and never in myxoid liposarcoma, cytogenetic analysis or FISH for the PLAG1 gene can provide useful differential diagnostic information.
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| 2. |
- Gisselsson Nord, David, et al.
(författare)
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Generation of trisomies in cancer cells by multipolar mitosis and incomplete cytokinesis.
- 2010
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 107:47, s. 20489-20493
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Tidskriftsartikel (refereegranskat)abstract
- One extra chromosome copy (i.e., trisomy) is the most common type of chromosome aberration in cancer cells. The mechanisms behind the generation of trisomies in tumor cells are largely unknown, although it has been suggested that dysfunction of the spindle assembly checkpoint (SAC) leads to an accumulation of trisomies through failure to correctly segregate sister chromatids in successive cell divisions. By using Wilms tumor as a model for cancers with trisomies, we now show that trisomic cells can form even in the presence of a functional SAC through tripolar cell divisions in which sister chromatid separation proceeds in a regular fashion, but cytokinesis failure nevertheless leads to an asymmetrical segregation of chromosomes into two daughter cells. A model for the generation of trisomies by such asymmetrical cell division accurately predicted several features of clones having extra chromosomes in vivo, including the ratio between trisomies and tetrasomies and the observation that different trisomies found in the same tumor occupy identical proportions of cells and colocalize in tumor tissue. Our findings provide an experimentally validated model explaining how multiple trisomies can occur in tumor cells that still maintain accurate sister chromatid separation at metaphase-anaphase transition and thereby physiologically satisfy the SAC.
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| 3. |
- Persson, Oscar, et al.
(författare)
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Microarray analysis of gliomas reveals chromosomal position-associated gene expression patterns and identifies potential immunotherapy targets.
- 2007
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Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 1573-7373 .- 0167-594X. ; 85:J1, s. 11-24
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Tidskriftsartikel (refereegranskat)abstract
- Gliomas are among the most aggressive malignant tumors and the most refractory to therapy, in part due to the propensity for malignant cells to disseminate diffusely throughout the brain. Here, we have used 27 K cDNA microarrays to investigate global gene expression changes between normal brain and high-grade glioma (glioblastoma multiforme) to try and better understand gliomagenesis and to identify new therapeutic targets. We have also included smaller groups of grade II and grade III tumors of mixed astrocytic and oligodendroglial origin as comparison. We found that the expression of hundreds of genes was significantly correlated to each group, and employed a naive Bayesian classifier with leave-one-out cross-validation to accurately classify the samples. We developed a novel algorithm to analyze the gene expression data from the perspective of chromosomal position, and identified distinct regions of the genome that displayed coordinated expression patterns that correlated significantly to tumor grade. The regions identified corresponded to previously known genetic copy number changes in glioma (e.g. 10q23, 10q25, 7q, 7p) as well as regions not previously associated significantly with glioma (e.g. 1p13, 6p22). Furthermore, to enrich for more suitable targets for therapy, we took a bioinformatics approach and annotated our signatures with two published datasets that identified membrane/secreted genes from cytosolic genes. The resulting focused list of 31 genes included interesting novel potential targets as well as several proteins already being investigated for immunotherapy (e.g. CD44 and tenascin-C). Software for the chromosome analysis was developed and is freely available at http://base.thep.lu.se.
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| 4. |
- Mertens, Fredrik, et al.
(författare)
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Prognostically important chromosomal aberrations in soft tissue sarcomas: a report of the Chromosomes and Morphology (CHAMP) Study Group.
- 2002
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Ingår i: Cancer Research. - 1538-7445. ; 62:14, s. 3980-3984
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Tidskriftsartikel (refereegranskat)abstract
- Cytogenetic analysis has not only provided important information on the pathogenesis of soft tissue tumors but, by disclosing distinct chromosomal rearrangements in different histopathological entities, has also come to serve as a valuable diagnostic tool. Little is known as yet about the potential prognostic impact of cytogenetic features detected in these tumors. A total of 239 benign and 221 malignant soft tissue tumors with clonal chromosome aberrations were subdivided according to general karyotypic features, such as degree of complexity and ploidy level, and rearrangements of specific chromosomal regions. The cytogenetic variables were analyzed regarding clinical outcome, using time to metastasis as the end point. Selected variables were then compared with established clinicopathological predictors of metastasis development. When the entire material was considered, 167 of 268 investigated cytogenetic variables were associated with clinical outcome. Focusing on the subset of 151 patients with high-grade sarcoma, 17 variables were identified that, besides grade and size, were associated with increased risk of metastasis development. A final Cox regression analysis identified five independent cytogenetic predictors of adverse outcome; breakpoints in chromosome regions 1p1, 1q4, 14q1, and 17q2, and gain of regions 6p1/p2. An increasing effect on metastatic risk was seen with increasing involvement of the selected cytogenetic variables, even when different histopathological types were studied separately. We conclude that cytogenetic data provide independent prognostic information in soft tissue sarcomas. Furthermore, our results point to specific areas of the genome harboring genes that may influence the metastatic potential of sarcoma cells.
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| 5. |
- Mandahl, Nils, et al.
(författare)
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Scattered genomic amplification in dedifferentiated liposarcoma
- 2017
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Ingår i: Molecular Cytogenetics. - : Springer Science and Business Media LLC. - 1755-8166. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Atypical lipomatous tumor (ALT), well differentiated liposarcoma (WDLS) and dedifferentiated liposarcoma (DDLS) are cytogenetically characterized by near-diploid karyotypes with no or few other aberrations than supernumerary ring or giant marker chromosomes, although DDLS tend to have somewhat more complex rearrangements. In contrast, pleomorphic liposarcomas (PLS) have highly aberrant and heterogeneous karyotypes. The ring and giant marker chromosomes contain discontinuous amplicons, in particular including multiple copies of the target genes CDK4, HMGA2 and MDM2 from 12q, but often also sequences from other chromosomes. Results: The present study presents a DDLS with an atypical hypertriploid karyotype without any ring or giant marker chromosomes. SNP array analyses revealed amplification of almost the entire 5p and discontinuous amplicons of 12q including the classical target genes, in particular CDK4. In addition, amplicons from 1q, 3q, 7p, 9p, 11q and 20q, covering from 2 to 14 Mb, were present. FISH analyses showed that sequences from 5p and 12q were scattered, separately or together, over more than 10 chromosomes of varying size. At RNA sequencing, significantly elevated expression, compared to myxoid liposarcomas, was seen for TRIO and AMACR in 5p and of CDK4, HMGA2 and MDM2 in 12q. Conclusions: The observed pattern of scattered amplification does not show the characteristics of chromothripsis, but is novel and differs from the well known cytogenetic manifestations of amplification, i.e., double minutes, homogeneously staining regions and ring chromosomes. Possible explanations for this unusual distribution of amplified sequences might be the mechanism of alternative lengthening of telomeres that is frequently active in DDLS and events associated with telomere crisis.
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| 6. |
- Bartuma, Hammurabi, et al.
(författare)
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Fusion of the FUS and CREB3L2 genes in a supernumerary ring chromosome in low-grade fibromyxoid sarcoma.
- 2010
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Ingår i: Cancer Genetics and Cytogenetics. - : Elsevier BV. - 0165-4608. ; 199:2, s. 143-146
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Tidskriftsartikel (refereegranskat)abstract
- Low-grade fibromyxoid sarcoma (LGFMS) is a rare, low-grade malignant soft tissue tumor that is often mistaken for either benign or more malignant tumor types. Commonly, this tumor affects young adults and typically arises in the deep proximal extremities or trunk with frequent recurrences and can metastasize to the lungs many years later. Most cases have a recurrent balanced translocation involving chromosomes 7 and 16, t(7;16)(q32-34;p11), which leads to the fusion of the FUS and CREB3L2 genes. However, supernumerary ring chromosomes have been identified in a subset of FUS/CREB3L2-positive LGFMS, but it has not yet been formally demonstrated that such ring chromosomes harbor the FUS/CREB3L2 fusion gene. Here, we report the genetic findings of a supernumerary ring chromosome from an LGFMS from a 77-year-old man. Chromosome banding analysis revealed a supernumerary ring chromosome, and further studies with fluorescence in situ hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR) showed that the ring contained material from chromosomes 7 and 16, that the FUS gene was present in two rearranged copies, and that it expressed the FUS/CREB3L2 fusion gene. Moreover, an assessment of previously reported cases showed that tumors with ring chromosomes relapsed more often than tumors with a balanced t(7;16), suggesting that ring formation in LGFMS is correlated with tumor progression.
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| 7. |
- Johnsson, Anna, et al.
(författare)
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Unstable translocation (8;22) in a case of giant cell reparative granuloma.
- 2007
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Ingår i: Cancer Genetics and Cytogenetics. - : Elsevier BV. - 0165-4608. ; 177:1, s. 59-63
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Tidskriftsartikel (refereegranskat)abstract
- Giant cell reparative granuloma (GCRG) is an uncommon lesion most often affecting the jaw but also the small bones of the hands and feet. GCRG overlaps clinically and radiographically with other giant cell-rich tumors such as giant cell tumor of bone (GCTB) and aneurysmal bone cyst (ABC). In the only case of a cytogenetically investigated GCRG reported previously, a balanced translocation involving chromosomes 4 and X was found. In the present study, chromosome banding and fluorescence in situ hybridization (FISH) analyses were used to characterize the primary lesion and local recurrence of a GCRG in the thumb and skin biopsy of a 45-year-old woman. The skin showed a normal karyotype. Various forms of a dic(8;22) containing 8q, 22q, and smaller or larger parts of 8p were found in both GCRG samples. In addition, ring chromosomes, most often composed of chromosome I I material, and telomeric associations were found. The latter aberrations were more frequent in the primary lesion. Normal FISH signals were seen when using probes capable of detecting USP6 rearrangernents. The variant 8;22 aberrations were interpreted to originate from an unstable dic(8;22)(p23;p11) that gradually evolved into a functionally monocentric chromosome in the dominating subset of cell populations. We conclude that our case of GCRG shared several cytogenetic characteristics with GCTB but none with ABC. (c) 2007 Elsevier Inc. All rights reserved.
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| 8. |
- Mertens, Fredrik, et al.
(författare)
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Radiation-associated sarcomas are characterized by complex karyotypes with frequent rearrangements of chromosome arm 3p
- 2000
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Ingår i: Cancer Genetics and Cytogenetics. - 0165-4608. ; 116:2, s. 89-96
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Tidskriftsartikel (refereegranskat)abstract
- Ionizing radiation is a well-known risk factor for sarcoma development. To investigate whether radiation-associated sarcomas are characterized by chromosome aberrations that distinguish them from de novo sarcomas, we identified those patients in our series of more than 500 cytogenetically abnormal sarcomas that fulfilled the following criteria: (1) each patient should have been irradiated for another malignancy at least 3 years prior to the sarcoma diagnosis, and (2) the sarcoma should have developed within the field of radiation. Ten patients fulfilling these criteria could be retrieved (median age at sarcoma diagnosis was 55 years, range 17-79; median latency period between primary tumor and radiation-associated sarcoma was 9 years, range 4-30). The diagnoses were typical for radiation-associated sarcomas: 2 each of malignant fibrous histiocytoma, leiomyosarcoma, and pleomorphic sarcoma, and 1 each of osteosarcoma, fibrosarcoma, myxofibrosarcoma, and spindle cell sarcoma. All 10 cases had relatively complex karyotypes with multiple, mostly unbalanced, structural rearrangements, similar to what has been reported in de novo sarcomas of the corresponding histologic subtypes. The only cytogenetic features that were unusually frequent among the radiation-associated sarcomas were the finding of unrelated clones in 3 cases, and loss of material from chromosome arm 3p, in particular 3p21-3pter, in 8 cases. Loss of the same chromosome segment has been described in 4 of the 8 previously published cases of radiation-associated sarcomas that have been analyzed after short-term culturing, which makes this imbalance significantly (P < 0.001) more frequent among radiation-associated sarcomas (12 of 18 cases) than among unselected cases of the corresponding histologic subtypes (74 of 282 cases). In contrast to the cytogenetic results, no 3p deletions were detected among the 6 cases of the present series that could be analyzed by comparative genomic hybridization (CGH). The most frequent imbalance detected by CGH was gain of 15cen-q15 (3 cases), followed by loss of chromosome 13 and gain of 5p, and 7cen-q22, each detected in 2 cases.
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| 9. |
- Nilbert, Mef, et al.
(författare)
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Complex karyotypic changes, including rearrangements of 12q13 and 14q24, in two leiomyosarcomas
- 1990
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Ingår i: Cancer Genetics and Cytogenetics. - 0165-4608. ; 48:2, s. 217-223
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Tidskriftsartikel (refereegranskat)abstract
- Cytogenetic investigation of short-term cultures from two leiomyosarcomas revealed complex karyotypic changes in both cases. The first tumor, a subcutaneous leiomyosarcoma of the knee, had the karyotype 70-80,XY, +X, +Y, +1, +1, +2, +2, +3, +3, +4, +4, +7, +7, +8, +8, +9, +10, +15, +15, +16, +16, +18, +19, +20, +21, +21, +22, +22,t(?;5)(5;21)(?;q35p11;q11), t(?;5)(5;21)(?;q35p11;q11), +del(11)(q22),der(13)t(12;13)(q13;q22),der(14)t(9;14)(p11;p11), +14p+, +t(20;?)(q13;?), +t(20;?)(q13;?), +2 mar. A polyploidized clone with 120-150 chromosomes was also observed. DNA flow cytometry revealed only one abnormal peak, corresponding to a DNA index of 1.76. The other tumor, a uterine leiomyosarcoma, had the karyotype 61-67, X, -X, +1, +3, +5, +6, +7, +8, +9, +12, +13, +15, +t(1;1)(p32;q32), +der(1)t(1;8)(p13;q11), +del(2)(p11), +del(2)(q22), +del(2)(q22), +del(3)(p13), +i(5p),t(8;14)(q24;q24), +der(8)t(8;14) (q24;q24), +del(10)(p12),der(11)t(11;15)(p15;q11),t(16;?)(p13;?),t(16;?)(q24;?), der dic(17) (17pter----cen----17q25::hsr::17q25----cen----17pte r), +t(19;?)(p13;?), +der dic(20)(20pter----cen----20q12::hsr::20q12----cen----+ ++20pter), +mar. The DNA index was 1.59. The finding in these leiomyosarcomas of rearrangements of the same regions of chromosomes 12 and 14 that are involved in the tumor-specific t(12;14)(q14-15;q23-24) of uterine leiomyoma indicates that the same genes in 12q and 14q might be important in the pathogenesis of benign and malignant smooth muscle tumors.
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| 10. |
- Płaszczyca, Anna, et al.
(författare)
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Fusions involving protein kinase C and membrane-associated proteins in benign fibrous histiocytoma.
- 2014
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Ingår i: International Journal of Biochemistry & Cell Biology. - : Elsevier BV. - 1878-5875 .- 1357-2725. ; 53:Apr 8, s. 475-481
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Tidskriftsartikel (refereegranskat)abstract
- Benign fibrous histiocytoma (BFH) is a mesenchymal tumor that most often occurs in the skin (so-called dermatofibroma), but may also appear in soft tissues (so-called deep BFH) and in the skeleton (so-called non-ossifying fibroma). The origin of BFH is unknown, and it has been questioned whether it is a true neoplasm. Chromosome banding, fluorescence in situ hybridization, single nucleotide polymorphism arrays, RNA sequencing, RT-PCR and quantitative real-time PCR were used to search for recurrent somatic mutations in a series of BFH. BFHs were found to harbor recurrent fusions of genes encoding membrane-associated proteins (podoplanin, CD63 and LAMTOR1) with genes encoding protein kinase C (PKC) isoforms PRKCB and PRKCD. PKCs are serine-threonine kinases that through their many phosphorylation targets are implicated in a variety of cellular processes, as well as tumor development. When inactive, the amino-terminal, regulatory domain of PKCs suppresses the activity of their catalytic domain. Upon activation, which requires several steps, they typically translocate to cell membranes, where they interact with different signaling pathways. The detected PDPN-PRKCB, CD63-PRKCD and LAMTOR1-PRKCD gene fusions are all predicted to result in chimeric proteins consisting of the membrane-binding part of PDPN, CD63 or LAMTOR1 and the entire catalytic domain of the PKC. This novel pathogenetic mechanism should result in constitutive kinase activity at an ectopic location. The results show that BFH indeed is a true neoplasm, and that distorted PKC activity is essential for tumorigenesis. The findings also provide means to differentiate BFH from other skin and soft tissue tumors. This article is part of a Directed Issue entitled: Rare cancers.
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