title: FOXO1-FGFR1 fusion and amplification in a solid variant of alveolar rhabdomyosarcoma.
abstract: Rhabdomyosarcoma is the most common pediatric soft tissue malignancy. Two major subtypes, alveolar rhabdomyosarcoma and embryonal rhabdomyosarcoma, constitute 20 and 60% of all cases, respectively. Approximately 80% of alveolar rhabdomyosarcoma carry two signature chromosomal translocations, t(2;13)(q35;q14) resulting in PAX3-FOXO1 fusion, and t(1;13)(p36;q14) resulting in PAX7-FOXO1 fusion. Whether the remaining cases are truly negative for gene fusion has been questioned. We are reporting the case of a 9-month-old girl with a metastatic neck mass diagnosed histologically as solid variant alveolar rhabdomyosarcoma. Chromosome analysis showed a t(8;13;9)(p11.2;q14;9q32) three-way translocation as the sole clonal aberration. Fluorescent in situ hybridization (FISH) demonstrated a rearrangement at the FOXO1 locus and an amplification of its centromeric region. Single-nucleotide polymorphism-based microarray analysis illustrated a co-amplification of the FOXO1 gene at 13q14 and the FGFR1 gene at 8p12p11.2, suggesting formation and amplification of a chimerical FOXO1-FGFR1 gene. This is the first report to identify a novel fusion partner FGFR1 for the known anchor gene FOXO1 in alveolar rhabdomyosarcoma.
authors.affiliation: Department of Pathology and Laboratory Medicine, St Christopher's Hospital for Children, Philadelphia, PA, USA.
authors.forename: Jinglan
authors.initials: J
authors.lastname: Liu
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Guzman
authors.forename: Donna
authors.initials: D
authors.lastname: Pezanowski
authors.forename: Dilipkumar
authors.initials: D
authors.lastname: Patel
authors.forename: John
authors.initials: J
authors.lastname: Hauptman
authors.forename: Matthew
authors.initials: M
authors.lastname: Keisling
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Hou
authors.forename: Peter R
authors.initials: PR
authors.lastname: Papenhausen
authors.forename: Judy M
authors.initials: JM
authors.lastname: Pascasio
authors.forename: Hope H
authors.initials: HH
authors.lastname: Punnett
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Halligan
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: de Chadarévian
mesh_terms: D002882:Chromosomes, Human, Pair 13; D002898:Chromosomes, Human, Pair 8; D002899:Chromosomes, Human, Pair 9; D020732:Cytogenetic Analysis; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005784:Gene Amplification; D050939:Gene Fusion; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics* / Q000556:secondary; D014178:Translocation, Genetic
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1