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JMD 2006, Vol. 8, No. 2
Copyright © 2006 American Society for Investigative Pathology & Association for Molecular Pathology

Examination of Gene Fusion Status in Archival Samples of Alveolar Rhabdomyosarcoma Entered on the Intergroup Rhabdomyosarcoma Study-III Trial

A Report from the Children’s Oncology Group

Frederic G. Barr^*, Lynette M. Smith, James C. Lynch, Donna Strzelecki^*, David M. Parham, Stephen J. Qualman and Philip P. Breitfeld^¶

From the Department of Pathology and Laboratory Medicine, * University of Pennsylvania, Philadelphia, Pennsylvania; the Department of Preventive and Societal Medicine, Nebraska Medical Center, Omaha, Nebraska; the Departments of Pathology and Pediatrics, Arkansas Children’s Hospital and University of Arkansas for Medical Sciences, Little Rock, Arkansas; the Department of Laboratory Medicine, Columbus Children’s Hospital, Columbus, Ohio; and Pediatric Hematology-Oncology, ^¶ Duke University Medical Center, Durham, North Carolina

Alveolar rhabdomyosarcoma (ARMS) is a soft tissue cancer in which chromosomal translocations generate PAX3-FKHR and PAX7-FKHR gene fusions. To improve the approach for fusion detection in archival samples, we developed a real-time reverse transcriptase-polymerase chain reaction assay for these fusion transcripts. By incorporating consensus primers and gene-specific probes, both presence and subtype of the fusion were determined in one assay. We applied this approach to a convenience sample of 78 formalin-fixed, paraffin-embedded ARMS tumors from the Intergroup Rhabdomyosarcoma Study (IRS)-III clinical trial and obtained satisfactory results in 59 (76%) cases. The distribution of fusion types was 35 (59%) PAX3-FKHR, 11 (19%) PAX7-FKHR, and 13 fusion-negative (22%). In a subsequent clinical analysis, we found that IRS-III ARMS cases analyzed for fusion status had a significantly improved outcome compared to IRS-III ARMS cases that were not available for fusion analysis. The basis of this outcome could not be explained by known prognostic clinical factors, and multivariate analysis confirmed that our convenience sample was not representative of the whole IRS-III cohort. In conclusion, although these robust assays provide new opportunities for correlative studies of archival material, our first application illustrates an important limitation of using a convenience sample for molecular-clinical correlative studies.

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