Chromosomal imbalances in pleomorphic rhabdomyosarcomas and identification of the alveolar rhabdomyosarcoma-associated PAX3-FOXO1A fusion gene in one case

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∼p33 (71%), 7p (43%), 18/18q (43%), and 20/20p (43%), and the regions of loss were 10q23 (71%), 15q21∼q22 (57%), 3p, 5q32∼qter, and 13 (all 43%). Four of the seven cases had amplicons involving the regions 1p21∼p31, 1q21∼q25, 3p12, 3q26∼qtel, 4q28∼q31, 8q21∼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.