| 1. |
- Panagopoulos, I, et al.
(författare)
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Clinical impact of molecular and cytogenetic findings in synovial sarcoma
- 2001
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 31:4, s. 72-362
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Tidskriftsartikel (refereegranskat)abstract
- Synovial sarcoma is an aggressive soft-tissue tumor that accounts for up to 10% of soft-tissue sarcomas. Cytogenetically, synovial sarcoma is characterized by the t(X;18)(p11;q11), found in more than 95% of the tumors. This translocation results in rearrangements of the SYT gene in 18q11 and one of the SSX1, SSX2, or SSX4 genes in Xp11, creating a SYT/SSX1, SYT/SSX2, or SYT/SSX4 chimeric gene. It has been shown that patients with SYT/SSX1 fusion genes have a shorter metastasis-free survival than do patients with SYT/SSX2. Previous studies have also suggested that clonal evolution may be associated with disease progression. In the present study, RT-PCR analysis showed that all 64 examined synovial sarcomas from 54 patients had SYT-SSX chimeric genes. SYT/SSX1 was found in 40 tumors from 33 patients, SYT/SSX2 in 23 tumors from 20 patients, and SYT/SSX4 in one case. Two patients had variant SYT/SSX2 transcripts, with 57 bp and 141 bp inserts, respectively, between the known SYT and SSX2 sequences. Patients with tumors with SYT/SSX1 fusions had a higher risk of developing metastases compared to those with SYT/SSX2 fusions (P = 0.01). The reciprocal transcripts SSX1/SYT and SSX2/SYT were detected using nested PCR in 11 of the 40 samples with SYT/SSX1 and 5 of the 23 samples with SYT/SSX2, respectively. Among 20 blood samples, SYT/SSX1 and SYT/SSX2 were detected in one sample each. The t(X;18), or variants thereof, was found cytogenetically in all patients but three. Among 32 primary tumors, the t(X;18) or a variant translocation was the sole anomaly in 10. In contrast, of the seven metastatic lesions that were investigated prior to radiotherapy, only one had a t(X;18) as the sole anomaly; all other tumors displayed complex karyotypes. Cytogenetic complexity in primary tumors was, however, not associated with the development of metastases. Tumors with SYT/SSX2 less often (4/12 vs. 7/15) showed complex karyotypes than did tumors with SYT/SSX1, but the difference was not significant. Combining cytogenetic complexity and transcript data, we found that the subgroup of patients with tumors showing simple karyotypes and SYT/SSX2 fusion had the best clinical outcome (2/8 patients developed metastases), and those with tumors showing complex karyotypes together with SYT/SSX1 fusion the worst (6/7 patients developed metastases). This corresponded to 5-year metastasis-free survival rates of 0.58 and 0.0, respectively (P = 0.02).
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| 2. |
- Gorunova, Ludmila, et al.
(författare)
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Nonrandom chromosomal aberrations and cytogenetic heterogeneity in gallbladder carcinomas
- 1999
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Ingår i: Genes, Chromosomes and Cancer. - 1045-2257. ; 26:4, s. 21-312
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Tidskriftsartikel (refereegranskat)abstract
- Chromosome banding analysis of 11 short-term cultured gallbladder carcinomas revealed acquired clonal aberrations in seven tumors (five primary and two metastases). Three of these had one clone, whereas the remaining four were cytogenetically heterogeneous, displaying two to seven aberrant clones. Of a total of 21 abnormal clones, 18 had highly complex karyotypes and three exhibited simple numerical deviations. Double minutes and homogeneously staining regions were observed in one and two carcinomas, respectively. To characterize the karyotypic profile of gallbladder cancer more precisely, we have combined the present findings with our three previously reported cases, thereby providing the largest cytogenetic database on this tumor type to date. A total of 287 chromosomal breakpoints were identified, 251 of which were found in the present study. Chromosome 7 was rearranged most frequently, followed by chromosomes 1, 3, 11, 6, 5, and 8. The bands preferentially involved were 1p32, 1p36, 1q32, 3p21, 6p21, 7p13, 7q11, 7q32, 19p13, 19q13, and 22q13. Nine recurrent abnormalities could, for the first time, be identified in gallbladder carcinoma: del(3)(p13), i(5)(p10), del(6)(q13), del(9)(p13), del(16)(q22), del(17)(p11), i(17)(q10), del(19)(p13), and i(21)(q10). The most common partial or whole-arm gains involved 3q, 5p, 7p, 7q, 8q, 11q, 13q, and 17q, and the most frequent partial or whole-arm losses affected 3p, 4q, 5q, 9p, 10p, 10q, 11p, 14p, 14q, 15p, 17p, 19p, 21p, 21q, and Xp. These chromosomal aberrations and imbalances provide some starting points for molecular analyses of genomic regions that may harbor genes of pathogenetic importance in gallbladder carcinogenesis. Genes Chromosomes Cancer 26:312-321, 1999.
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| 3. |
- Parada, L A, et al.
(författare)
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Cytogenetics of hepatoblastoma: further characterization of 1q rearrangements by fluorescence in situ hybridization: an international collaborative study
- 2000
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Ingår i: Medical and Pediatric Oncology. - 1096-911X. ; 34:3, s. 165-170
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hepatoblastoma (HBT) is the most common hepatic neoplasm in children. This notwithstanding, little is known about pathogenetic factors, such as genetic abnormalities, of importance for the development and progression of this tumor type. To date, only 33 cytogenetically abnormal HBT have been published, and trisomies for chromosomes 2 and 20 have been shown to be the most frequent aberrations. Recently, unbalanced translocations involving proximal 1q have been described in several HBT, suggesting that a pathogenetically important gene maps to 1q. PROCEDURE: Six primary and one recurrent HBT were cytogenetically analyzed after short-term tissue culture. In addition, fluorescence in situ hybridization (FISH) studies, using locus-specific probes, were performed on three of these pediatric HBT as well as on one previously reported adult HBT. RESULTS: Total or partial trisomy 8, gain of chromosome 20, and structural rearrangements of chromosome 1 were detected in three HBT, and overrepresentation of chromosome 2 material was found in two HBT. The adjacent chromosome bands 1q12 and 1q21 were involved in three translocations, t(1;2), t(1;4), and t(1;11), which were all unbalanced and resulted in gain of 1q material. The previously reported adult HBT displayed 1q deletions with breakpoints at 1q12-21. FISH analyses of the 1q rearrangements revealed that all breakpoints were within the heterochromatic region. CONCLUSIONS: These findings provide further support for the importance of trisomies 2, 8, and 20 and rearrangements of 1q in the development of HBT. Furthermore, the consistent localization of breakpoints within the heterochromatic segment of chromosome 1 suggests that the important pathogenetic consequence of 1q abnormalities is the resulting genomic imbalance rather than a specific gene rearrangement.
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