title: Genomic Characterization of a Metastatic Alveolar Rhabdomyosarcoma Case Using FISH Studies and CGH+SNP Microarray Revealing FOXO1-PAX7 Rearrangement with MYCN and MDM2 Amplification and RB1 Region Loss.
abstract: Rhabdomyosarcomas (RMS) are rare, heterogeneous, soft tissue sarcomas and a common type of childhood malignancy with a distinct histomorphology. At the molecular level, alveolar rhabdomyosarcoma (ARMS), a subtype of RMS, harbors a signature genetic makeup characterized by specific translocations. The type of translocation and associated genetic aberrations correlate with disease progression, hence we used multiple molecular modalities including high-resolution array comparative genomic hybridization to explore the oncogenic gene fusion and associated copy number variations in a case of metastatic ARMS. We describe a case where traditional cytogenetic and molecular methods yielded inconclusive results in detecting the FOXO1 gene rearrangement. However, microarray analysis identified the essential FOXO1-PAX7 aberration and additional submicroscopic genomic alterations, including amplification of MYCN and MDM2 and deletion of RB1.
authors.affiliation: Department of Pathology, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Arivarasan
authors.initials: A
authors.lastname: Karunamurthy
authors.forename: Lori
authors.initials: L
authors.lastname: Hoffner
authors.forename: Jie
authors.initials: J
authors.lastname: Hu
authors.forename: Peter
authors.initials: P
authors.lastname: Shaw
authors.forename: Sarangarajan
authors.initials: S
authors.lastname: Ranganathan
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Yatsenko
authors.forename: Urvashi
authors.initials: U
authors.lastname: Surti
mesh_terms: D002648:Child; D055028:Comparative Genomic Hybridization; D000071161:Forkhead Box Protein O1 / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D000071447:N-Myc Proto-Oncogene Protein / Q000235:genetics*; D009362:Neoplasm Metastasis; D051763:PAX7 Transcription Factor / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D056286:Retinoblastoma Binding Proteins / Q000235:genetics*; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics* / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human; C000606393:RB1 protein, human; D056286:Retinoblastoma Binding Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D044767:Ubiquitin-Protein Ligases