Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1996 Feb;148(2):559–567.

Interphase fluorescence in situ hybridization and reverse transcription polymerase chain reaction as a diagnostic aid for synovial sarcoma.

J Shipley 1, J Crew 1, S Birdsall 1, S Gill 1, J Clark 1, C Fisher 1, A Kelsey 1, T Nojima 1, H Sonobe 1, C Cooper 1, B Gusterson 1
PMCID: PMC1861680  PMID: 8579118

Abstract

Identification of the t(X;18)(p11.2;q11.2) that is associated with a high proportion of synovial sarcoma can be a useful diagnostic aid. The translocation results in fusion of the SYT gene on chromosome 18 to either the SSX1 or the SSX2 gene, two homologous genes within Xp11.2. Two-color interphase fluorescence in situ hybridization and reverse transcription polymerase chain reaction were assessed as approaches to identify the rearrangement in well characterized cases. The presence of the translocation, and the specific chromosome X gene disrupted, were inferred from the configuration of signals from chromosome-specific centromere probes, paints, and markers flanking each gene in preparations of interphase nuclei. Rearrangement was found in two cell lines and eight of nine tumor samples, including analysis of five touch imprints. This was consistent with cytogenetic data in four cases and reverse transcription polymerase chain reaction analysis using primers known to amplify both SYT-SSX1 and SYT-SSX2 transcripts. The transcripts were distinguished by restriction with LspI and SmaI. Contrary to previous suggestions, there was no obvious correlation between histological subtype and involvement of the SSX1 or SSX2 gene. These approaches could also be applied to the identification of tumor-free margins and metastatic disease.

Full text

PDF
562

Images in this article

563Figure 1
on p.563
564Figure 3
on p.564

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Birdsall S. H., MacLennan K. A., Gusterson B. A. t(6;12)(q23;q13) and t(10;16)(q22;p11) in a phyllodes tumor of breast. Cancer Genet Cytogenet. 1992 May;60(1):74–77. doi: 10.1016/0165-4608(92)90236-2. [DOI] [PubMed] [Google Scholar]
  2. Borrow J., Shipley J., Howe K., Kiely F., Goddard A., Sheer D., Srivastava A., Antony A. C., Fioretos T., Mitelman F. Molecular analysis of simple variant translocations in acute promyelocytic leukemia. Genes Chromosomes Cancer. 1994 Apr;9(4):234–243. doi: 10.1002/gcc.2870090403. [DOI] [PubMed] [Google Scholar]
  3. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  4. Clark J., Rocques P. J., Crew A. J., Gill S., Shipley J., Chan A. M., Gusterson B. A., Cooper C. S. Identification of novel genes, SYT and SSX, involved in the t(X;18)(p11.2;q11.2) translocation found in human synovial sarcoma. Nat Genet. 1994 Aug;7(4):502–508. doi: 10.1038/ng0894-502. [DOI] [PubMed] [Google Scholar]
  5. Crew A. J., Clark J., Fisher C., Gill S., Grimer R., Chand A., Shipley J., Gusterson B. A., Cooper C. S. Fusion of SYT to two genes, SSX1 and SSX2, encoding proteins with homology to the Kruppel-associated box in human synovial sarcoma. EMBO J. 1995 May 15;14(10):2333–2340. doi: 10.1002/j.1460-2075.1995.tb07228.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Davis R. J., D'Cruz C. M., Lovell M. A., Biegel J. A., Barr F. G. Fusion of PAX7 to FKHR by the variant t(1;13)(p36;q14) translocation in alveolar rhabdomyosarcoma. Cancer Res. 1994 Jun 1;54(11):2869–2872. [PubMed] [Google Scholar]
  7. Delattre O., Zucman J., Melot T., Garau X. S., Zucker J. M., Lenoir G. M., Ambros P. F., Sheer D., Turc-Carel C., Triche T. J. The Ewing family of tumors--a subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med. 1994 Aug 4;331(5):294–299. doi: 10.1056/NEJM199408043310503. [DOI] [PubMed] [Google Scholar]
  8. Desmaze C., Zucman J., Delattre O., Melot T., Thomas G., Aurias A. Interphase molecular cytogenetics of Ewing's sarcoma and peripheral neuroepithelioma t(11;22) with flanking and overlapping cosmid probes. Cancer Genet Cytogenet. 1994 May;74(1):13–18. doi: 10.1016/0165-4608(94)90022-1. [DOI] [PubMed] [Google Scholar]
  9. Desmaze C., Zucman J., Delattre O., Thomas G., Aurias A. Unicolor and bicolor in situ hybridization in the diagnosis of peripheral neuroepithelioma and related tumors. Genes Chromosomes Cancer. 1992 Jul;5(1):30–34. doi: 10.1002/gcc.2870050105. [DOI] [PubMed] [Google Scholar]
  10. Fisher C. Synovial sarcoma: ultrastructural and immunohistochemical features of epithelial differentiation in monophasic and biphasic tumors. Hum Pathol. 1986 Oct;17(10):996–1008. doi: 10.1016/s0046-8177(86)80083-1. [DOI] [PubMed] [Google Scholar]
  11. Galili N., Davis R. J., Fredericks W. J., Mukhopadhyay S., Rauscher F. J., 3rd, Emanuel B. S., Rovera G., Barr F. G. Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nat Genet. 1993 Nov;5(3):230–235. doi: 10.1038/ng1193-230. [DOI] [PubMed] [Google Scholar]
  12. Janz M., De Leeuw B., Weghuis D. O., Werner M., Nolte M., Geurts Van Kessel A., Nordheim A., Hipskind R. A. Interphase cytogenetic analysis of distinct X-chromosomal translocation breakpoints in synovial sarcoma. J Pathol. 1995 Apr;175(4):391–396. doi: 10.1002/path.1711750405. [DOI] [PubMed] [Google Scholar]
  13. Jeon I. S., Davis J. N., Braun B. S., Sublett J. E., Roussel M. F., Denny C. T., Shapiro D. N. A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1. Oncogene. 1995 Mar 16;10(6):1229–1234. [PubMed] [Google Scholar]
  14. Lee W., Han K., Harris C. P., Shim S., Kim S., Meisner L. F. Use of FISH to detect chromosomal translocations and deletions. Analysis of chromosome rearrangement in synovial sarcoma cells from paraffin-embedded specimens. Am J Pathol. 1993 Jul;143(1):15–19. [PMC free article] [PubMed] [Google Scholar]
  15. Limon J., Dal Cin P., Sandberg A. A. Translocations involving the X chromosome in solid tumors: presentation of two sarcomas with t(X;18)(q13;p11). Cancer Genet Cytogenet. 1986 Sep;23(1):87–91. doi: 10.1016/0165-4608(86)90152-4. [DOI] [PubMed] [Google Scholar]
  16. Limon J., Mrozek K., Mandahl N., Nedoszytko B., Verhest A., Rys J., Niezabitowski A., Babinska M., Nosek H., Ochalek T. Cytogenetics of synovial sarcoma: presentation of ten new cases and review of the literature. Genes Chromosomes Cancer. 1991 Sep;3(5):338–345. doi: 10.1002/gcc.2870030504. [DOI] [PubMed] [Google Scholar]
  17. McManus A. P., Gusterson B. A., Pinkerton C. R., Shipley J. M. Diagnosis of Ewing's sarcoma and related tumours by detection of chromosome 22q12 translocations using fluorescence in situ hybridization on tumour touch imprints. J Pathol. 1995 Jun;176(2):137–142. doi: 10.1002/path.1711760206. [DOI] [PubMed] [Google Scholar]
  18. Nagao K., Gomyo Y., Ito H., Yamamoto K., Yoshida H. A case report of synovial sarcoma with translocation (X;18). Application of fluorescence in situ hybridization to paraffin-embedded tissue. Virchows Arch. 1995;426(5):519–522. doi: 10.1007/BF00193176. [DOI] [PubMed] [Google Scholar]
  19. Olde Weghuis D., Stoepker M. E., de Leeuw B., van den Berg E., Suijkerbuijk R. F., Molenaar W. M., de Jong B., Geurts van Kessel A. A synovial sarcoma with a complex t(X;18;5;4) and a break in the ornithine aminotransferase (OAT)L1 cluster on Xp11.2. Genes Chromosomes Cancer. 1994 Apr;9(4):288–291. doi: 10.1002/gcc.2870090409. [DOI] [PubMed] [Google Scholar]
  20. PACK G. T., ARIEL I. M. Synovial sarcoma (malignant synovioma); a report of 60 cases. Surgery. 1950 Dec;28(6):1047–1084. [PubMed] [Google Scholar]
  21. Renwick P. J., Reeves B. R., Dal Cin P., Fletcher C. D., Kempski H., Sciot R., Kazmierczak B., Jani K., Sonobe H., Knight J. C. Two categories of synovial sarcoma defined by divergent chromosome translocation breakpoints in Xp11.2, with implications for the histologic sub-classification of synovial sarcoma. Cytogenet Cell Genet. 1995;70(1-2):58–63. doi: 10.1159/000133992. [DOI] [PubMed] [Google Scholar]
  22. Sandberg A. A., Turc-Carel C. The cytogenetics of solid tumors. Relation to diagnosis, classification and pathology. Cancer. 1987 Feb 1;59(3):387–395. doi: 10.1002/1097-0142(19870201)59:3<387::aid-cncr2820590306>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  23. Shipley J. M., Clark J., Crew A. J., Birdsall S., Rocques P. J., Gill S., Chelly J., Monaco A. P., Abe S., Gusterson B. A. The t(X;18)(p11.2;q11.2) translocation found in human synovial sarcomas involves two distinct loci on the X chromosome. Oncogene. 1994 May;9(5):1447–1453. [PubMed] [Google Scholar]
  24. Shipley J. M., Jones T. A., Patel K., Kiely F. M., De Stavola B. L., Sheer D. Ordering of probes surrounding the Ewing's sarcoma breakpoint on chromosome 22 using fluorescent in situ hybridization to interphase nuclei. Cytogenet Cell Genet. 1993;64(3-4):233–239. doi: 10.1159/000133585. [DOI] [PubMed] [Google Scholar]
  25. Smith S., Reeves B. R., Wong L., Fisher C. A consistent chromosome translocation in synovial sarcoma. Cancer Genet Cytogenet. 1987 May;26(1):179–180. doi: 10.1016/0165-4608(87)90147-6. [DOI] [PubMed] [Google Scholar]
  26. Sonobe H., Manabe Y., Furihata M., Iwata J., Oka T., Ohtsuki Y., Mizobuchi H., Yamamoto H., Kumano O., Abe S. Establishment and characterization of a new human synovial sarcoma cell line, HS-SY-II. Lab Invest. 1992 Oct;67(4):498–505. [PubMed] [Google Scholar]
  27. Sreekantaiah C., Ladanyi M., Rodriguez E., Chaganti R. S. Chromosomal aberrations in soft tissue tumors. Relevance to diagnosis, classification, and molecular mechanisms. Am J Pathol. 1994 Jun;144(6):1121–1134. [PMC free article] [PubMed] [Google Scholar]
  28. Turc-Carel C., Dal Cin P., Limon J., Li F., Sandberg A. A. Translocation X;18 in synovial sarcoma. Cancer Genet Cytogenet. 1986 Sep;23(1):93–93. doi: 10.1016/0165-4608(86)90153-6. [DOI] [PubMed] [Google Scholar]
  29. Wilkinson M. RNA isolation: a mini-prep method. Nucleic Acids Res. 1988 Nov 25;16(22):10933–10933. doi: 10.1093/nar/16.22.10933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Zucman J., Melot T., Desmaze C., Ghysdael J., Plougastel B., Peter M., Zucker J. M., Triche T. J., Sheer D., Turc-Carel C. Combinatorial generation of variable fusion proteins in the Ewing family of tumours. EMBO J. 1993 Dec;12(12):4481–4487. doi: 10.1002/j.1460-2075.1993.tb06137.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. de Leeuw B., Suijkerbuijk R. F., Olde Weghuis D., Meloni A. M., Stenman G., Kindblom L. G., Balemans M., van den Berg E., Molenaar W. M., Sandberg A. A. Distinct Xp11.2 breakpoint regions in synovial sarcoma revealed by metaphase and interphase FISH: relationship to histologic subtypes. Cancer Genet Cytogenet. 1994 Apr;73(2):89–94. doi: 10.1016/0165-4608(94)90191-0. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES