1.
Dahlén, A, et al.
(author)
Analysis of the distribution and frequency of trisomy 7 in vivo in synovia from patients with osteoarthritis and pigmented villonodular synovitis
2001
In: Cancer Genetics and Cytogenetics. - 0165-4608. ; 131:1, s. 19-24
Journal article (peer-reviewed) abstract
Osteoarthritis (OA) and pigmented villonodular synovitis (PVNS) are disorders associated with trisomy 7. The aim of the present study was to determine the frequency and distribution of the cells with +7 in vivo by analyzing sections of paraffin-embedded synovia from patients affected by OA, PVNS, other forms of synovitis [hemorragic synovitis (HS) and chronic synovitis (CS)], and from individuals without joint disease. Fluorescence in situ hybridization (FISH), using a centromeric probe for chromosome 7, showed that the mean frequency of trisomic nuclei in 5-microm sections was highest in PVNS (9.0%), followed by CS (5.9%), OA (5.6%), and HS (4.6%), whereas trisomic nuclei were rare (0.7%) in normal tissue. When 8-microm sections were studied, the frequencies of trisomic cells in OA and control synovia increased to 6.7% and 1.5%, respectively. Trisomic nuclei were found in all cases, including those for which cytogenetic analysis of short-term cultures had not disclosed any trisomic cells. Overall, the trisomic cells were scattered within the tissue. However, small clusters of cells with +7 were found in three cases. By hematoxylin-eosin staining of the slides used for FISH analysis it could be shown that the clustered trisomic cells were proliferating synoviocytes within villous extensions of the synovial membrane.
2.
Gisselsson, D, et al.
(author)
Abnormal nuclear shape in solid tumors reflects mitotic instability
2001
In: American Journal of Pathology. - 1525-2191. ; 158:1, s. 199-206
Journal article (peer-reviewed) abstract
Abnormalities in nuclear morphology are frequently observed in malignant tissues but the mechanisms behind these phenomena are still poorly understood. In this study, the relation between abnormal nuclear shape and chromosomal instability was explored in short-term tumor cell cultures. Mitotically unstable ring and dicentric chromosomes were identified by fluorescence in situ hybridization at metaphase and subsequently localized in interphase nuclei from five malignant soft tissue tumors. The vast majority (71 to 86%) of nuclear blebs, chromatin strings, and micronuclei contained material from the unstable chromosomes, whereas few (<11%) were positive for stable chromosomes. Nuclear morphology was also evaluated in fibroblasts and an osteosarcoma cell line exposed to irradiation. A linear correlation was found between the frequency of abnormalities in nuclear shape, on one hand, and cells with unstable chromosomes (r = 0.87) and anaphase bridge configurations (r = 0.98), on the other hand. The relation between nuclear shape and karyotypic pattern was investigated further in cultures from 58 tumors of bone, soft tissue, and epithelium. Blebs, strings, and micronuclei were significantly more frequent in tumors that contained rings, dicentrics, or telomeric associations than in those exhibiting only stable aberrations (P: < 0.001) and a positive correlation (r = 0.78) was found between the frequency of such nuclear abnormalities and the intratumor heterogeneity of structural chromosome aberrations. These results indicate that the formation of nuclear blebs, chromatin strings, and micronuclei in malignant tissues is closely related to the breakage-fusion-bridge type of mitotic disturbances. Abnormalities in nuclear shape may thus primarily be regarded as an indicator of genetic instability and intratumor heterogeneity, independent of cytogenetic complexity and the grade of malignancy.
3.
Panagopoulos, I, et al.
(author)
Clinical impact of molecular and cytogenetic findings in synovial sarcoma
2001
In: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 31:4, s. 72-362
Journal article (peer-reviewed) 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).
