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| 2. |
- 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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| 3. |
- 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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| 5. |
- Panagopoulos, Ioannis, et al.
(författare)
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Molecular genetic characterization of the EWS/CHN and RBP56/CHN fusion genes in extraskeletal myxoid chondrosarcoma.
- 2002
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 35:4, s. 340-352
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Tidskriftsartikel (refereegranskat)abstract
- Extraskeletal myxoid chondrosarcoma (EMC) is a soft-tissue neoplasm cytogenetically characterized by the translocations t(9;22)(q22;q11-12) or t(9;17)(q22;q11), generating EWS/CHN or RBP56/CHN fusion genes, respectively. In the present study, 18 EMCs were studied both cytogenetically and at the molecular level. Chromosomal aberrations were detected in 16 samples: 13 with involvement of 9q22 and 22q11-12, and three with rearrangements of 9q22 and 17q11. Fifteen cases had an EWS/CHN fusion transcript and three had an RBP56/CHN transcript. The most frequent EWS/CHN transcript (type 1; 10 tumors), involved fusion of EWS exon 12 with CHN exon 3, and the second most common (type 5; two cases) was fusion of EWS exon 13 with CHN exon 3. In all tumors with RBP56/CHN fusion, exon 6 of RBP56 was fused to exon 3 of CHN. By genomic XL PCR and sequence analyses, the breakpoints from 14 cases were mapped in the EWS, RBP56, and CHN genes. In CHN, 12 breakpoints were found in intron 2 and only two in intron 1. In EWS, the breaks occurred in introns 7 (one break), 12 (eight breaks), and 13 (one break), and in RBP56 in intron 6. Repetitive elements such as Alu and LINE sequences seem to have limited, if any, importance in the genesis of EWS/CHN and RBP56/CHN chimeras. Furthermore, there were no chi, chi-like, topoisomerase II, or translin consensus sequences in the introns harboring the translocation breakpoints, nor could the number of topo I sites in EWS, RBP56, and CHN introns explain the uneven distribution of the breakpoints among EWS or CHN introns. Additional genetic events, such as nucleotide insertions, homologies at the junction, deletions, duplications, and inversions, were found to accompany the translocations, indicating that the chromosomal translocations do not require sequence-specific recombinases or extensive homology between the recombined sequences. Copyright 2002 Wiley-Liss, Inc.
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| 6. |
- Storlazzi, Tiziana, et al.
(författare)
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A novel fusion gene, SS18L1/SSX1, in synovial sarcoma
- 2003
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 37:2, s. 195-200
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Tidskriftsartikel (refereegranskat)abstract
- Synovial sarcoma is an aggressive soft tissue tumor that is characterized cytogenetically by the t(X;18)(p11;q11) translocation, resulting in fusion between the SS18 gene on chromosome 18 and one of the SSX genes on the X chromosome. The three fusion genes that have been detected thus far, SS18/SSX1, SS18/SSX2, and SS18/SSX4, account for more than 95% of the synovial sarcomas. Because SS18/SSX fusions do not seem to occur in other tumor types, and because synovial sarcomas may sometimes be difficult to distinguish from other spindle cell tumors, molecular genetic analysis has become established as an important diagnostic tool. Upon cytogenetic analysis of a soft-tissue tumor that showed classic synovial sarcoma morphology, we detected two supernumerary marker chromosomes but no rearrangement of chromosomes X or 18. By fluorescence in situ hybridization, the marker chromosomes were shown to contain material from chromosomes X and 20, including the SSX gene cluster on the X chromosome and the SS18L1 gene, which shows strong homology with the SS18 gene, on chromosome 20. Further RT-PCR analysis and sequencing of the amplified products revealed a novel SS18L1/SSX1 fusion transcript in which nucleotide 1216 (exon 10) of SS18L1 was fused in-frame with nucleotide 422 (exon 6) of SSX1. Thus, the existence of genetic heterogeneity has to be taken into account when RT-PCR is used for the diagnosis of synovial sarcoma.
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