title: Chromosomal imbalances in pleomorphic rhabdomyosarcomas and identification of the alveolar rhabdomyosarcoma-associated PAX3-FOXO1A fusion gene in one case.
abstract: Rhabdomyosarcomas (RMS) are soft tissue sarcomas resembling developing skeletal muscle, and pleomorphic rhabdomyosarcomas (PRMS) are a rare nonpediatric entity. Little molecular cytogenetic information exists for PRMS, and their relationship to other subtypes of rhabdomyosarcoma and other sarcomas is unclear. Chromosomal imbalances were determined in seven well-characterized cases of PRMS using comparative genomic hybridization. The smallest overlapping regions of gain were 1p22 approximately p33 (71%), 7p (43%), 18/18q (43%), and 20/20p (43%), and the regions of loss were 10q23 (71%), 15q21 approximately q22 (57%), 3p, 5q32 approximately qter, and 13 (all 43%). Four of the seven cases had amplicons involving the regions 1p21 approximately p31, 1q21 approximately q25, 3p12, 3q26 approximately qtel, 4q28 approximately q31, 8q21 approximately q23/8q, and 22q. These regions are distinct from those frequently associated with the alveolar subtype, whereas the embryonal subtype without anaplasia is rarely associated with amplification events other than gain/amplification of 8q material. The regions of imbalance appeared more similar to those reported for malignant fibrous histiocytomas (MFH) and osteosarcomas, consistent with the suggestion that PRMS can be considered part of the spectrum of MFH. In addition, one of the cases classified as PRMS showed evidence for the presence of a PAX3-FOXO1A fusion gene, which is characteristic of the alveolar subtype of RMS.
authors.affiliation: Section of Molecular Carcinogenesis, Molecular Cytogenetics Laboratory, Institute of Cancer Research, Sutton, UK SM2 5NG, Surrey, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Gordon
authors.forename: Aidan
authors.initials: A
authors.lastname: McManus
authors.forename: John
authors.initials: J
authors.lastname: Anderson
authors.forename: Cyril
authors.initials: C
authors.lastname: Fisher
authors.forename: Syuiti
authors.initials: S
authors.lastname: Abe
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nojima
authors.forename: Kathy
authors.initials: K
authors.lastname: Pritchard-Jones
authors.forename: Janet
authors.initials: J
authors.lastname: Shipley
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D018219:Histiocytoma, Benign Fibrous / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012208:Rhabdomyosarcoma / Q000145:classification / Q000235:genetics* / Q000473:pathology; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics; D012983:Soft Tissue Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D015514:Oncogene Proteins, Fusion; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; C471563:PAX3-FOXO1A fusion protein, human; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C068686:Pax3 protein, mouse