title: Cryptic insertion of 3'FOXO1 into inverted chromosome arm 2q in the presence of two normal chromosome 13s and 13 small interstitial duplications in a patient with alveolar rhabdomyosarcoma.
abstract: Alveolar rhabdomyosarcoma (ARMS) is a pediatric soft tissue neoplasm with a characteristic translocation, t(2;13)(q35;q14), which is detected in 70-80% of cases. This well-described translocation produces the gene fusion product PAX3-FOXO1. Cryptic rearrangements of this fusion have never before been reported in ARMS. Here we describe a patient with ARMS that showed, by fluorescence in situ hybridization and G-banded chromosomes, a cryptic insertion of 3'FOXO1 into inverted chromosome 2q. The inversion breakpoints were depicted by array comparative genomic hybridization as two small interstitial duplications, one of which involved the PAX3 gene. In addition, the array comparative genomic hybridization results revealed 1q gain, 16q loss, and 11 more small duplications, with one of them involving the FOXO1 gene. Although the pathogenesis in classic ARMS cases is thought to be driven by the 5'PAX3-3'FOXO1 fusion on derivative chromosome 13, here we report a novel cryptic insertion of 3'FOXO1 resulting in a pathogenic fusion with 5'PAX3 on inverted chromosome 2q.
authors: Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, St. Louis, MO, USA.
authors: Sarah
authors: S
authors: Hackman
authors: Molecular Cytogenetics Department, SSM Cardinal Glennon Children's Medical Center, St. Louis, MO, USA.
authors: Laura
authors: L
authors: Calvey
authors: Molecular Cytogenetics Department, SSM Cardinal Glennon Children's Medical Center, St. Louis, MO, USA.
authors: Kristen
authors: K
authors: Bernreuter
authors: Molecular Cytogenetics Department, SSM Cardinal Glennon Children's Medical Center, St. Louis, MO, USA.
authors: Mengya Wang
authors: MW
authors: Mark
authors: Pathology and Pediatric Departments, Saint Louis University Medical Center, St. Louis, MO, USA.
authors: Sarah
authors: S
authors: Starnes
authors: Molecular Cytogenetics Department, SSM Cardinal Glennon Children's Medical Center, St. Louis, MO, USA; Pathology and Pediatric Departments, Saint Louis University Medical Center, St. Louis, MO, USA. Electronic address: Batanijr@Slu.edu.
authors: Jacqueline R
authors: JR
authors: Batanian
mesh_terms: D002675:Child, Preschool; D058674:Chromosome Duplication; D007446:Chromosome Inversion; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006801:Humans; D054643:INDEL Mutation; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008297:Male; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics*
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors
keywords: 3′FOXO1; Alveolar rhabdomyosarcoma; Cryptic fusion