| 1. |
- 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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| 2. |
- Broberg Palmgren, Karin, et al.
(författare)
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Fusion of RDC1 with HMGA2 in lipomas as the result of chromosome aberrations involving 2q35-37 and 12q13-15.
- 2002
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Ingår i: International Journal of Oncology. - 1019-6439. ; 21:2, s. 321-326
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Tidskriftsartikel (refereegranskat)abstract
- Rearrangements of chromosome bands 12q13-15 are frequent in various benign mesenchymal and epithelial tumors, and the gene HMGA2 seems to be the most common target within this chromosome region. In the majority of cases, the rearrangements result in a fusion of the first three exons of HMGA2 with different translocation partners. Despite the large number of HMGA2 mutations that have been reported, very little is known about the fusion partners. In this study, we have characterized a recurrent fusion of the first three exons of HMGA2 5' to the G protein-coupled receptor gene (RDC1) in lipomas with rearrangements involving chromosome bands 2q35-37 and 12q13-15, one of several recurrent chromosomal rearrangements in lipomas. The functional impact of the fusion is truncation of HMGA2, because the RDC1 part contributes with a stop codon one amino acid downstream of the breakpoint. The breakpoint within RDC1 was localized in a previously uncharacterized exon of the gene, and our data suggest that RDC1 is subject to alternative splicing.
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| 3. |
- Crnalic, S, et al.
(författare)
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Establishment and characterisation of a human clear cell sarcoma model in nude mice
- 2002
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 101:6, s. 505-511
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Tidskriftsartikel (refereegranskat)abstract
- We have established a new experimental model of human clear cell sarcoma, UM-CCSI, using serial subcutaneous transplantation of intact tumour tissue in nude mice. The heterotransplanted nude mouse tumours retained characteristic morphological features of the primary clear cell sarcoma. Immunohistochemical analysis showed the retained expression patterns of S-100 protein, melanoma-associated antigen HMB-45 and vimentin in the xenografts as compared to the primary tumour. DNA index showed low variations both between the xenografts in the same passage and between the serial passages. Cytogenetic analysis of the primary tumour and the xenografts showed the unbalanced translocation der(6)t(6; I 2)(p23;q13). Based on the combined genetic data a reasonable interpretation of our findings is that there was a complex chromosomal rearrangement resulting in a cytogenetically cryptic EWS-ATFI fusion gene. Analysis of cell kinetics using in vivo incorporation of iododeoxyuridine and flow cytometry showed generally short potential doubling time (T-pot) of the xenografts. Volume doubling time showed low variations without correlation with T-pot. The retained phenotypic and genotypic characteristics of the primary tumour and the morphological and structural stability over time makes the model suitable for studies on the tumour biology and treatment of clear cell sarcoma. (C) 2002 Wiley-Liss, Inc.
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| 4. |
- Dahlén, Anna, et al.
(författare)
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Clustering of deletions on chromosome 13 in benign and low-malignant lipomatous tumors
- 2003
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 103:5, s. 616-623
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Tidskriftsartikel (refereegranskat)abstract
- Deletions and structural rearrangements of the long arm of chromosome 13 are frequently observed in benign and low-malignant lipomatous tumors, but nothing is known about their molecular genetic consequences. We assessed the karyotypes of 40 new and 22 previously published cases (35 ordinary lipomas, 15 spindle cell/pleomorphic lipomas, 2 myxolipomas, 1 angiomyxolipoma and 9 atypical lipomatous tumors) with chromosome 13-abnormalities, and found bands 13q12-22 to be frequently affected. Twenty-seven cases with structural abnormalities within this region were selected for breakpoint and deletion mapping by metaphase fluorescence in situ hybridization (FISH), using a set of 20 probes. Deletions were found in 23 of 27 cases. The remaining 4 cases had seemingly balanced rearrangements. The breakpoints were scattered but clustered to band 13q14, and in all cases with unbalanced abnormalities, a limited region within band 13q14 was partially or completely deleted. A deletion within band 13q14 was found together with a breakpoint on the other homologue in 5 cases, 4 of which could be tested further with regard to the status of the retinoblastoma (RB1)-gene. In all 4 cases, only 1 copy of the gene was deleted. In addition to the breaks and deletions in the vicinity of the RB1-locus, several other regions of 13q were recurrently affected, e.g., in the vicinity of the hereditary breast cancer (BRCA2; 13q12)- and lipoma HMGIC fusion partner (LHFP; 13q13)- genes. Our findings strongly indicate that deletion of a limited region (approximately 2.5 Mbp) within 13q14, distal to the RB1-locus, is of importance in the development of a subset of lipomatous tumors.
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| 5. |
- Elmula, Imad, et al.
(författare)
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Chromosomal aberrations in benign and malignant Bilharzia-associated bladder lesions analyzed by comparative genomic hybridization.
- 2002
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 2:5
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Fadl-Elmula, Imad, et al.
(författare)
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Characterization of chromosomal abnormalities in uroepithelial carcinomas by G-banding, spectral karyotyping and fish analysis
- 2001
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 92:6, s. 824-831
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Gisselsson Nord, David, et al.
(författare)
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Differentially amplified chromosome 12 sequences in low- and high-grade osteosarcoma.
- 2002
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 33:2, s. 133-140
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Tidskriftsartikel (refereegranskat)abstract
- Most osteosarcomas are highly aggressive malignancies characterized by a complex pattern of chromosome abnormalities. However, a subgroup of low-grade, parosteal tumors exhibits a relatively simple aberration pattern dominated by ring chromosomes carrying amplified material from chromosome 12. To assess whether sequences from this chromosome were differentially amplified in low- and high-grade osteosarcomas, copy numbers of the CCND2, ETV6, KRAS2, and D12S85 regions in 12p and the MDM2 region in 12q were evaluated by interphase or metaphase fluorescence in situ hybridization (FISH) in 24 osteosarcomas. Amplification of MDM2 was detected in all five low-grade and four high-grade osteosarcomas, all of which showed ring chromosomes. An overrepresentation of 12p sequences was found in 1/5 low-grade and in 9/19 high-grade tumors. Multicolor single-copy FISH analysis of metaphase cells from six high-grade tumors showed that extra 12p material either occurred together with MDM2 in ring chromosomes or was scattered over the genome as a result of complex structural rearrangements. Most tumors (8/10) not containing amplification of the assessed chromosome 12 loci exhibited a nondiploid pattern at evaluation with probes for centromeric alpha satellite sequences. These findings indicate that gain of sequences from the short arm of chromosome 12 could be a possible genetic pathway in the development of aggressive osteosarcoma.
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| 8. |
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| 9. |
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| 10. |
- Kuźniacka, Alina, et al.
(författare)
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Combined binary ratio labeling fluorescence in situ hybridization analysis of chordoma
- 2004
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Ingår i: Cancer Genetics and Cytogenetics. - : Elsevier BV. - 0165-4608. ; 151:2, s. 178-181
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Tidskriftsartikel (refereegranskat)abstract
- Chordoma is a rare, low- to intermediate-grade malignant tumor involving the axial spine. Cytogenetic data on these tumors have been limited to 25 cases. The findings of clonal chromosome aberrations in five new cases are presented. One of these and two previously reported cases have been studied with multicolor combined binary ratio labeling fluorescence in situ hybridization (COBRA-FISH). The karyotypes were near-diploid, mostly with several numerical and structural aberrations. There were multiple imbalances, with loss of segments from 1p, 3p, 3q, 9p, and chromosome 10 seen in two to four of the seven cases. No clustering of breakpoints was seen and no recurrent recombination between chromosomes was detected. The findings are consistent with previous data and indicate that chordoma tumor development is associated with multiple, nonrandom losses including chromosome segments that are frequently involved in many other solid tumors.
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