Clinical impact of molecular and cytogenetic findings in synovial sarcoma
(2001) In Genes, Chromosomes and Cancer 31(4). p.72-362- 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... (More)
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).
(Less)
- author
- organization
- publishing date
- 2001-08
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adolescent, Adult, Aged, Aged, 80 and over, Amino Acid Sequence, Base Sequence, Child, Female, Humans, Karyotyping, Male, Middle Aged, Molecular Sequence Data, Neoplasm Proteins, Oncogene Proteins, Fusion, Proteins, Proto-Oncogene Proteins, Repressor Proteins, Sarcoma, Synovial, Sequence Analysis, DNA, Soft Tissue Neoplasms, Journal Article, Research Support, Non-U.S. Gov't
- in
- Genes, Chromosomes and Cancer
- volume
- 31
- issue
- 4
- pages
- 11 pages
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:11433527
- scopus:0034938146
- pmid:11433527
- ISSN
- 1045-2257
- DOI
- 10.1002/gcc.1155
- language
- English
- LU publication?
- yes
- id
- 922fb88b-c459-4011-8876-fd94a5170d0e (old id 1122195)
- date added to LUP
- 2016-04-01 12:15:58
- date last changed
- 2022-01-27 01:12:01
@article{922fb88b-c459-4011-8876-fd94a5170d0e,
abstract = {{<p>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).</p>}},
author = {{Panagopoulos, I and Mertens, F and Isaksson, Margareth and Limon, J and Gustafson, Pelle and Skytting, B and Åkerman, Måns and Sciot, R and Dal Cin, P and Samson, I and Iliszko, M and Ryoe, J and Dêbiec-Rychter, M and Szadowska, A and Brosjö, O and Larsson, O and Rydholm, A and Mandahl, N}},
issn = {{1045-2257}},
keywords = {{Adolescent; Adult; Aged; Aged, 80 and over; Amino Acid Sequence; Base Sequence; Child; Female; Humans; Karyotyping; Male; Middle Aged; Molecular Sequence Data; Neoplasm Proteins; Oncogene Proteins, Fusion; Proteins; Proto-Oncogene Proteins; Repressor Proteins; Sarcoma, Synovial; Sequence Analysis, DNA; Soft Tissue Neoplasms; Journal Article; Research Support, Non-U.S. Gov't}},
language = {{eng}},
number = {{4}},
pages = {{72--362}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Genes, Chromosomes and Cancer}},
title = {{Clinical impact of molecular and cytogenetic findings in synovial sarcoma}},
url = {{http://dx.doi.org/10.1002/gcc.1155}},
doi = {{10.1002/gcc.1155}},
volume = {{31}},
year = {{2001}},
}