| 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. |
- Jin, Charlotte, et al.
(författare)
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Karyotypic heterogeneity and clonal evolution in squamous cell carcinomas of the head and neck.
- 2002
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Ingår i: Cancer Genetics and Cytogenetics. - 0165-4608. ; 132:2, s. 85-96
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Tidskriftsartikel (refereegranskat)abstract
- Head and neck squamous cell carcinomas (HNSCC) are often characterized by complex karyotypic changes, and a substantial proportion of the reported tumors have shown intratumor heterogeneity in the form of cytogenetically related (40%) or unrelated clones (20%). In order to study intratumor heterogeneity and to distinguish the temporal order of chromosome rearrangements in these tumors, two or more samples from different areas of the same tumor were separately examined in 19 HNSCC, yielding karyotypes from a total of 42 tumor samples. Intrasample heterogeneity was observed in 16 samples. Two samples displayed both related and unrelated multiple clones, four samples showed only multiple unrelated clones, and the remaining 10 samples had only related subclones. Intersample heterogeneity was detected in all but one tumor. Five tumors showed both cytogenetically related and unrelated multiple clones, 11 were found to have only related subclones, and the remaining two tumors showed only unrelated clones. Clonal evolution could be assessed in 13 tumors. A comparison of chromosome imbalances in different subclones from these tumors suggests that partial or entire loss of 3p, 8p, 9p, and 18q and gain of genetic material from 3q and 8q are likely to be early genetic events. In contrast, loss of 1q, 6p, 7q, and chromosome 10, as well as gain of chromosome arms 5p and 7p, are most probably later genetic events. One of the examined tumors contained two highly complex clones that were cytogenetically unrelated, indicating that this tumor had a multicellular origin.
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| 3. |
- Adeyinka, Adewale, et al.
(författare)
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Comparative cytogenetic and DNA flow cytometric analysis of 242 primary breast carcinomas
- 2003
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Ingår i: Cancer Genetics and Cytogenetics. - 0165-4608. ; 147:1, s. 62-67
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Tidskriftsartikel (refereegranskat)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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| 4. |
- 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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| 5. |
- 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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| 6. |
- Domanski, Henryk, et al.
(författare)
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Distinct cytologic features of spindle cell lipoma - A cytologic-histologic study with clinical, radiologic, electron microscopic, and cytogenetic correlations
- 2001
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Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 93:6, s. 381-389
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Spindle cell lipoma (SCL) is a relatively uncommon, benign tumor that usually presents in the subcutaneous fat of adult men. Although some studies have addressed the histologic findings of SCL, only a few descriptions of aspiration cytology findings have been published. The cytologic features are poorly defined, and aspirates from SCL may cause diagnostic problems, because SCL shares some features with other fatty/spindle cell or myxoid lesions, benign as well as malignant. METHODS. Twelve patients underwent fine-needle aspiration (FNA) cytology as the primary diagnostic modality before surgery. FNA findings were evaluated and correlated with histologic features, In addition, radiologic, electron microscopic, and cytogenetic findings were analyzed. The objective of this study was to determine cytologic criteria of SCL by reviewing cytologic specimens in 12 patients with SCL who underwent FNA cytology. RESULTS. All of the motors arose in adults, and to tumors developed in the subcutaneous tissue of the neck, back, or shoulder girdle. Two patients presented with tumors in atypical locations; one in the tongue and one in the check. Cytologically, all 12 tumors were characterized by a mixture of mature adipocytes, uniform spindle cells, and collagen bundles and/or fibers in varying proportions. The presence of a myxoid matrix and of mast cells was less specific and occurred in six aspirates. CONCLUSIONS. SCL has a characteristic cytologic appearance that, together with clinical data, helps to exclude low-grade liposarcoma as well as other spindle cell and myxoid lesions.
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| 7. |
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| 8. |
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| 9. |
- 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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