Journal of Clinical Oncology, Vol 15, 1831-1836, Copyright © 1997 by American Society of Clinical Oncology

ARTICLES

Common and variant gene fusions predict distinct clinical phenotypes in rhabdomyosarcoma

KM Kelly, RB Womer, PH Sorensen, QB Xiong and FG Barr
Division of Oncology, Children's Hospital of Philadelphia, PA, USA.

PURPOSE: We evaluated the clinical features of the common PAX3-FKHR and variant PAX7-FKHR gene fusions observed in rhabdomyosarcoma. PATIENTS AND METHODS: Reverse-transcriptase polymerase chain reaction (RT-PCR) assays were used to detect the gene fusions in 34 cases of rhabdomyosarcoma. Clinical data were obtained retrospectively and compared with the molecular results. RESULTS: The PAX3-FKHR and PAX7- FKHR gene fusions were present in tumors from 18 and 16 patients, respectively. The group with a PAX7-FKHR fusion was younger (P = .01) and presented more often with an extremity lesion (82% v 22%; P = .001). PAX7-FKHR tumors were more often localized than PAX3-FKHR tumors (P = .03). In patients with metastatic disease at diagnosis, the patterns were different: PAX7-FKHR patients had metastatic disease that involved only bone (n = 2) and distant nodes (n = 2), while the PAX3- FKHR group had multiple sites involved, including bone (n = 7), marrow (n = 7), lungs (n = 3), distant nodes (n = 2), skin (n = 1), and brain (n = 1). No significant difference in relapse rate was observed. A trend toward improved overall survival in the PAX7-FKHR group was noted (P = .09). Event-free survival for this PAX7-FKHR group was significantly longer (P = .04). CONCLUSION: Our results suggest that the common PAX3-FKHR and the variant PAX7-FKHR fusions are associated with distinct clinical phenotypes. Identification of fusion gene status may be a useful diagnostic tool in rhabdomyosarcoma.

This article has been cited by other articles:

				O. Slater and J. Shipley Clinical relevance of molecular genetics to paediatric sarcomas J. Clin. Pathol., November 1, 2007; 60(11): 1187 - 1194. [Abstract] [Full Text] [PDF]

				H. J. Siegel, G. S. Connor, D. Lee, R. Lopez-Ben, and D. R. Kelly Synchronous bifocal alveolar rhabdomyosarcoma: A CASE REPORT J Bone Joint Surg Br, July 1, 2006; 88-B(7): 955 - 958. [Abstract] [Full Text] [PDF]

				A. M. Oliveira and C. D.M. Fletcher Molecular Prognostication for Soft Tissue Sarcomas: Are We Ready Yet? J. Clin. Oncol., October 15, 2004; 22(20): 4031 - 4034. [Full Text] [PDF]

				A. M. Friedmann, N. J. Tarbell, P. W. Schaefer, and B. L. Hoch Case 4-2004 - A Nine-Month-Old Boy with an Orbital Rhabdomyosarcoma N. Engl. J. Med., January 29, 2004; 350(5): 494 - 502. [Full Text] [PDF]

				H P McDowell Update on childhood rhabdomyosarcoma Arch. Dis. Child., April 1, 2003; 88(4): 354 - 357. [Abstract] [Full Text] [PDF]

				T. Hosaka, Y. Nakashima, K. Kusuzaki, H. Murata, T. Nakayama, T. Nakamata, T. Aoyama, T. Okamoto, K. Nishijo, N. Araki, et al. A Novel Type of EWS-CHOP Fusion Gene in Two Cases of Myxoid Liposarcoma J. Mol. Diagn., August 1, 2002; 4(3): 164 - 171. [Abstract] [Full Text] [PDF]

				P. H.B. Sorensen, J. C. Lynch, S. J. Qualman, R. Tirabosco, J. F. Lim, H. M. Maurer, J. A. Bridge, W. M. Crist, T. J. Triche, and F. G. Barr PAX3-FKHR and PAX7-FKHR Gene Fusions Are Prognostic Indicators in Alveolar Rhabdomyosarcoma: A Report From the Children's Oncology Group J. Clin. Oncol., June 1, 2002; 20(11): 2672 - 2679. [Abstract] [Full Text] [PDF]

				M. Ladanyi, C. R. Antonescu, D. H. Leung, J. M. Woodruff, A. Kawai, J. H. Healey, M. F. Brennan, J. A. Bridge, J. R. Neff, F. G. Barr, et al. Impact of SYT-SSX Fusion Type on the Clinical Behavior of Synovial Sarcoma: A Multi-Institutional Retrospective Study of 243 Patients Cancer Res., January 1, 2002; 62(1): 135 - 140. [Abstract] [Full Text] [PDF]

				C. R. Antonescu, S. J. Tschernyavsky, R. Decuseara, D. H. Leung, J. M. Woodruff, M. F. Brennan, J. A. Bridge, J. R. Neff, J. R. Goldblum, and M. Ladanyi Prognostic Impact of P53 Status, TLS-CHOP Fusion Transcript Structure, and Histological Grade in Myxoid Liposarcoma: A Molecular and Clinicopathologic Study of 82 Cases Clin. Cancer Res., December 1, 2001; 7(12): 3977 - 3987. [Abstract] [Full Text] [PDF]

				L. M. Smith, J. R. Anderson, S. J. Qualman, W. M. Crist, C. N. Paidas, L. A. Teot, A. S. Pappo, M. P. Link, H. E. Grier, E. S. Wiener, et al. Which Patients With Microscopic Disease and Rhabdomyosarcoma Experience Relapse After Therapy? A Report From the Soft Tissue Sarcoma Committee of the Children's Oncology Group J. Clin. Oncol., October 15, 2001; 19(20): 4058 - 4064. [Abstract] [Full Text] [PDF]

				J. Anderson, A. Ramsay, S. Gould, and K. Pritchard-Jones PAX3-FKHR Induces Morphological Change and Enhances Cellular Proliferation and Invasion in Rhabdomyosarcoma Am. J. Pathol., September 1, 2001; 159(3): 1089 - 1096. [Abstract] [Full Text] [PDF]

				Y.-J. Lu, D. Williamson, J. Clark, R. Wang, N. Tiffin, L. Skelton, T. Gordon, R. Williams, B. Allan, A. Jackman, et al. Comparative expressed sequence hybridization to chromosomes for tumor classification and identification of genomic regions of differential gene expression PNAS, July 31, 2001; 98(16): 9197 - 9202. [Abstract] [Full Text] [PDF]

				W. M. Crist, J. R. Anderson, J. L. Meza, C. Fryer, R. B. Raney, F. B. Ruymann, J. Breneman, S. J. Qualman, E. Wiener, M. Wharam, et al. Intergroup Rhabdomyosarcoma Study-IV: Results for Patients With Nonmetastatic Disease J. Clin. Oncol., June 15, 2001; 19(12): 3091 - 3102. [Abstract] [Full Text] [PDF]

				E. de Alava and J. Pardo Ewing Tumor: Tumor Biology and Clinical Applications International Journal of Surgical Pathology, January 1, 2001; 9(1): 7 - 17. [Abstract] [PDF]

				M. Ladanyi Diagnosis and Classification of Small Round-Cell Tumors of Childhood Am. J. Pathol., December 1, 1999; 155(6): 2181 - 2182. [Full Text] [PDF]

				C. A.S. Arndt and W. M. Crist Common Musculoskeletal Tumors of Childhood and Adolescence N. Engl. J. Med., July 29, 1999; 341(5): 342 - 352. [Full Text] [PDF]

				J. P. Ginsberg, E. de Alava, M. Ladanyi, L. H. Wexler, H. Kovar, M. Paulussen, A. Zoubek, B. Dockhorn-Dworniczak, H. Juergens, J. S. Wunder, et al. EWS-FLI1 and EWS-ERG Gene Fusions Are Associated With Similar Clinical Phenotypes in Ewing's Sarcoma J. Clin. Oncol., June 1, 1999; 17(6): 1809 - 1809. [Abstract] [Full Text] [PDF]

				R. Dagher and L. Helman Rhabdomyosarcoma: An Overview Oncologist, February 1, 1999; 4(1): 34 - 44. [Abstract] [Full Text]

				A. Kawai, J. Woodruff, J. H. Healey, M. F. Brennan, C. R. Antonescu, and M. Ladanyi SYT-SSX Gene Fusion as a Determinant of Morphology and Prognosis in Synovial Sarcoma N. Engl. J. Med., January 15, 1998; 338(3): 153 - 160. [Abstract] [Full Text] [PDF]

				H. H. Zhao, R. E. Herrera, E. Coronado-Heinsohn, M. C. Yang, J. H. Ludes-Meyers, K. J. Seybold-Tilson, Z. Nawaz, D. Yee, F. G. Barr, S. G. Diab, et al. Forkhead Homologue in Rhabdomyosarcoma Functions as a Bifunctional Nuclear Receptor-interacting Protein with Both Coactivator and Corepressor Functions J. Biol. Chem., July 20, 2001; 276(30): 27907 - 27912. [Abstract] [Full Text] [PDF]