Novel genomic imbalances in embryonal rhabdomyosarcoma revealed by comparative genomic hybridization and fluorescence in situ hybridization: An intergroup rhabdomyosarcoma study

A comparative genomic hybridization (CGH) approach provides identification of genomic gains and losses in a tumor specimen in a single experiment. Onl y II embryonal rhabdomyosarcomas (E-RMS) have previously been subjected to CGH. The underlying genetic events in this histologic subtype are not well defined. In this investigation, 12 E-RMS specimens from 10 patients entered into Intergroup Rhabdomyosarcoma Study (IRS) I-IV and two local patients:w ere analyzed by CGH and fluorescence in situ hybridization (FISH). Gains of chromosomes or chromosomal regions 2 (50%), 7 (42%), 8 (67%), 11 (42%), 12 (58%), 13q21 (33%), and 20 (33%) and losses of 1p35-36.3 (42%), 6 (33%), 9 q22 (33%), 14q21-32 (25%), and 17 (25%) were most prominent. Chromosomal re gions 1p35-36.3 and 9q22 represent novel regions of loss. Importantly, loss of 9q22 corresponds to the locus of a putative tumor suppressor gene (PTCH ), which has been shown to play a role in rhabdomyosarcoma in a mouse model of Gorlin syndrome. Loss of 1p36 corresponds to the locus for PAX7, a pair ed box containing gene characteristically altered in alveolar rhabdomyosarc oma. Moreover, loss of 1p36 is prominent In another common pediatric soft t issue tumor, neuroblastoma. Gains of 2, 7, 8, 12, and 13 and loss of 14 wer e seen in the sole prior E-RMS CGH series; thus, these data provide importa nt confirmatory results. In contrast to this previous study, however loss, not gain, of chromosome 17 was observed in the current study. Chromosome 17 loss correlates well with previous descriptions of frequent allelic loss o f 17p (TP53) in E-RMS. In summary, CGH and FISH analyses of 12 E-RMS specim ens revealed novel genomic imbalances that may be useful in directing furth er molecular studies for the determination of E-RMS critically involved gen es. (C) 2000 Wiley-Liss, Inc.