Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 2001 Sep;85(6):831–835. doi: 10.1054/bjoc.2001.2008

Detection of the PAX3-FKHR fusion gene in paediatric rhabdomyosarcoma: a reproducible predictor of outcome?

J Anderson 1,1,1, T Gordon 1,2, A McManus 1,2, T Mapp 3, S Gould 5, A Kelsey 6, H McDowell 4, R Pinkerton 1, J Shipley 2, K Pritchard-Jones 1; (on behalf of the UK Children's Cancer Study Group (UKCCSG) and the UK Cancer Cytogenetics Group)1
PMCID: PMC2375077  PMID: 11556833

Abstract

Rhabdomyosarcoma has 2 major histological subtypes, embryonal and alveolar. Alveolar histology is associated with the fusion genes PAX3-FKHR and PAX7-FKHR. Definition of alveolar has been complicated by changes in terminology and subjectivity. It is currently unclear whether adverse clinical behaviour is better predicted by the presence of these fusion genes or by alveolar histology. We have determined the presence of the PAX3/7-FKHR fusion genes in 91 primary rhabdomyosarcoma tumours using a combination of classical cytogenetics, FISH and RT-PCR, with a view to determining the clinical characteristics of tumours with and without the characteristic translocations. There were 37 patients with t(2;13)/PAX3-FKHR, 8 with t(1;13) PAX7-FKHR and 46 with neither translocation. One or other of the characteristic translocations was found in 31/38 (82%) of alveolar cases. Univariate survival analysis revealed the presence of the translocation t(2;13)/PAX3-FKHR to be an adverse prognostic factor. With the difficulties in morphological diagnosis of alveolar rhabdomyosarcoma on increasingly used small needle biopsy specimens, these data suggest that molecular analysis for PAX3-FKHR will be a clinically useful tool in treatment stratification in the future. This hypothesis requires testing in a prospective study. Variant t(1;13)/PAX7-FKHR appears biologically different, occurring in younger patients with more localised disease. © 2001 Cancer Research Campaignhttp://www.bjcancer.com

Keywords: rhabdomyosarcoma, prognosis, translocation

Full Text

The Full Text of this article is available as a PDF (55.6 KB).

Selected References

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

  1. Anderson J., Renshaw J., McManus A., Carter R., Mitchell C., Adams S., Pritchard-Jones K. Amplification of the t(2; 13) and t(1; 13) translocations of alveolar rhabdomyosarcoma in small formalin-fixed biopsies using a modified reverse transcriptase polymerase chain reaction. Am J Pathol. 1997 Feb;150(2):477–482. [PMC free article] [PubMed] [Google Scholar]
  2. Bennicelli J. L., Fredericks W. J., Wilson R. B., Rauscher F. J., 3rd, Barr F. G. Wild type PAX3 protein and the PAX3-FKHR fusion protein of alveolar rhabdomyosarcoma contain potent, structurally distinct transcriptional activation domains. Oncogene. 1995 Jul 6;11(1):119–130. [PubMed] [Google Scholar]
  3. Biegel J. A., Nycum L. M., Valentine V., Barr F. G., Shapiro D. N. Detection of the t(2;13)(q35;q14) and PAX3-FKHR fusion in alveolar rhabdomyosarcoma by fluorescence in situ hybridization. Genes Chromosomes Cancer. 1995 Mar;12(3):186–192. doi: 10.1002/gcc.2870120305. [DOI] [PubMed] [Google Scholar]
  4. Bown N. P., Reid M. M., Malcolm A. J., Davison E. V., Craft A. W., Pearson A. D. Cytogenetic abnormalities of small round cell tumours. Med Pediatr Oncol. 1994;23(2):124–129. doi: 10.1002/mpo.2950230210. [DOI] [PubMed] [Google Scholar]
  5. Crist W. M., Garnsey L., Beltangady M. S., Gehan E., Ruymann F., Webber B., Hays D. M., Wharam M., Maurer H. M. Prognosis in children with rhabdomyosarcoma: a report of the intergroup rhabdomyosarcoma studies I and II. Intergroup Rhabdomyosarcoma Committee. J Clin Oncol. 1990 Mar;8(3):443–452. doi: 10.1200/JCO.1990.8.3.443. [DOI] [PubMed] [Google Scholar]
  6. Crist W., Gehan E. A., Ragab A. H., Dickman P. S., Donaldson S. S., Fryer C., Hammond D., Hays D. M., Herrmann J., Heyn R. The Third Intergroup Rhabdomyosarcoma Study. J Clin Oncol. 1995 Mar;13(3):610–630. doi: 10.1200/JCO.1995.13.3.610. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Douglass E. C., Shapiro D. N., Valentine M., Rowe S. T., Carroll A. J., Raney R. B., Ragab A. H., Abella S. M., Parham D. M. Alveolar rhabdomyosarcoma with the t(2;13): cytogenetic findings and clinicopathologic correlations. Med Pediatr Oncol. 1993;21(2):83–87. doi: 10.1002/mpo.2950210202. [DOI] [PubMed] [Google Scholar]
  9. Downing J. R., Khandekar A., Shurtleff S. A., Head D. R., Parham D. M., Webber B. L., Pappo A. S., Hulshof M. G., Conn W. P., Shapiro D. N. Multiplex RT-PCR assay for the differential diagnosis of alveolar rhabdomyosarcoma and Ewing's sarcoma. Am J Pathol. 1995 Mar;146(3):626–634. [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Gordon T., McManus A., Anderson J., Min T., Swansbury J., Pritchard-Jones K., Shipley J., United kingdom Children's Cancer Study Group. United Kingdom Cancer Cytogenetics Group Cytogenetic abnormalities in 42 rhabdomyosarcoma: a United Kingdom Cancer Cytogenetics Group Study. Med Pediatr Oncol. 2001 Feb;36(2):259–267. doi: 10.1002/1096-911X(20010201)36:2<259::AID-MPO1063>3.0.CO;2-K. [DOI] [PubMed] [Google Scholar]
  12. Kelly K. M., Womer R. B., Sorensen P. H., Xiong Q. B., Barr F. G. Common and variant gene fusions predict distinct clinical phenotypes in rhabdomyosarcoma. J Clin Oncol. 1997 May;15(5):1831–1836. doi: 10.1200/JCO.1997.15.5.1831. [DOI] [PubMed] [Google Scholar]
  13. McManus A. P., Min T., Swansbury G. J., Gusterson B. A., Pinkerton C. R., Shipley J. M. der(16)t(1;16)(q21;q13) as a secondary change in alveolar rhabdomyosarcoma. A case report and review of the literature. Cancer Genet Cytogenet. 1996 Apr;87(2):179–181. doi: 10.1016/0165-4608(95)00267-7. [DOI] [PubMed] [Google Scholar]
  14. McManus A. P., O'Reilly M. A., Jones K. P., Gusterson B. A., Mitchell C. D., Pinkerton C. R., Shipley J. M. Interphase fluorescence in situ hybridization detection of t(2;13)(q35;q14) in alveolar rhabdomyosarcoma--a diagnostic tool in minimally invasive biopsies. J Pathol. 1996 Apr;178(4):410–414. doi: 10.1002/(SICI)1096-9896(199604)178:4<410::AID-PATH508>3.0.CO;2-A. [DOI] [PubMed] [Google Scholar]
  15. Pinkerton C. R., Groot-Loonen J., Barrett A., Meller S. T., Tait D., Ashley S., McElwain T. J. Rapid VAC high dose melphalan regimen, a novel chemotherapy approach in childhood soft tissue sarcomas. Br J Cancer. 1991 Aug;64(2):381–385. doi: 10.1038/bjc.1991.313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Roberts P., Browne C. F., Lewis I. J., Bailey C. C., Spicer R. D., Williams J., Batcup G. 12q13 abnormality in rhabdomyosarcoma. A nonrandom occurrence? Cancer Genet Cytogenet. 1992 Jun;60(2):135–140. doi: 10.1016/0165-4608(92)90005-s. [DOI] [PubMed] [Google Scholar]
  17. Scrable H., Witte D., Shimada H., Seemayer T., Sheng W. W., Soukup S., Koufos A., Houghton P., Lampkin B., Cavenee W. Molecular differential pathology of rhabdomyosarcoma. Genes Chromosomes Cancer. 1989 Sep;1(1):23–35. doi: 10.1002/gcc.2870010106. [DOI] [PubMed] [Google Scholar]
  18. Tsokos M., Webber B. L., Parham D. M., Wesley R. A., Miser A., Miser J. S., Etcubanas E., Kinsella T., Grayson J., Glatstein E. Rhabdomyosarcoma. A new classification scheme related to prognosis. Arch Pathol Lab Med. 1992 Aug;116(8):847–855. [PubMed] [Google Scholar]
  19. Valentine M., Douglass E. C., Look A. T. Closely linked loci on the long arm of chromosome 13 flank a specific 2;13 translocation breakpoint in childhood rhabdomyosarcoma. Cytogenet Cell Genet. 1989;52(3-4):128–132. doi: 10.1159/000132861. [DOI] [PubMed] [Google Scholar]
  20. Weber-Hall S., McManus A., Anderson J., Nojima T., Abe S., Pritchard-Jones K., Shipley J. Novel formation and amplification of the PAX7-FKHR fusion gene in a case of alveolar rhabdomyosarcoma. Genes Chromosomes Cancer. 1996 Sep;17(1):7–13. doi: 10.1002/(SICI)1098-2264(199609)17:1<7::AID-GCC2>3.0.CO;2-0. [DOI] [PubMed] [Google Scholar]
  21. Yule S. M., Bown N., Malcolm A. J., Reid M. M., Pearson A. D. Solid alveolar rhabdomyosarcoma with a t(2;13). Cancer Genet Cytogenet. 1995 Apr;80(2):107–109. doi: 10.1016/0165-4608(94)00170-g. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES