title: Detection of the PAX3-FKHR fusion gene in paediatric rhabdomyosarcoma: a reproducible predictor of outcome?
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.
authors.affiliation: Section of Paediatric Oncology, Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: J
authors.initials: J
authors.lastname: Anderson
authors.forename: T
authors.initials: T
authors.lastname: Gordon
authors.forename: A
authors.initials: A
authors.lastname: McManus
authors.forename: T
authors.initials: T
authors.lastname: Mapp
authors.forename: S
authors.initials: S
authors.lastname: Gould
authors.forename: A
authors.initials: A
authors.lastname: Kelsey
authors.forename: H
authors.initials: H
authors.lastname: McDowell
authors.forename: R
authors.initials: R
authors.lastname: Pinkerton
authors.forename: J
authors.initials: J
authors.lastname: Shipley
authors.forename: K
authors.initials: K
authors.lastname: Pritchard-Jones
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019677:Artificial Gene Fusion; D002648:Child; D002675:Child, Preschool; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D009124:Muscle Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D000072041:PAX3 Transcription Factor; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018232:Rhabdomyosarcoma, Alveolar / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D018233:Rhabdomyosarcoma, Embryonal / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C068686:Pax3 protein, mouse