FOXO1–FGFR1 fusion and amplification in a solid variant of alveolar rhabdomyosarcoma

• Published in: Modern pathology 2011-10, Vol.24 (10), p.1327-1335
• Main Authors: Liu, Jinglan, Guzman, Miguel A, Pezanowski, Donna, Patel, Dilipkumar, Hauptman, John, Keisling, Matthew, Hou, Steve J, Papenhausen, Peter R, Pascasio, Judy M, Punnett, Hope H, Halligan, Gregory E, de Chadarévian, Jean-Pierre
• Format: Article
• Language: English
• Subjects: 631/208/737/1505; 692/699/67/1798; 692/700/139/422; Chromosomes; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 8; Chromosomes, Human, Pair 9; Cloning; Cytogenetic Analysis; Female; Forkhead Box Protein O1; Forkhead Transcription Factors - genetics; Gene Amplification; Gene Fusion; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - pathology; Humans; In Situ Hybridization, Fluorescence; Infant; Laboratories; Laboratory Medicine; Lymphatic system; Medicine; Medicine & Public Health; Oligonucleotide Array Sequence Analysis; Oncology; original-article; Pathology; Pediatrics; Polymorphism; Polymorphism, Single Nucleotide; Receptor, Fibroblast Growth Factor, Type 1 - genetics; Rhabdomyosarcoma, Alveolar - genetics; Rhabdomyosarcoma, Alveolar - secondary; Translocation, Genetic
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/modpathol.2011.98

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.