NOVEL GENOMIC IMBALANCES IN EMBRYONAL RHABDOMYOSARCOMA REVEALED BY COMPARATIVE GENOMIC HYBRIDIZATION AND FLUORESCENCE IN SITU HYBRIDIZATION

Bridge JA, Lui J, Weibolt V, Baker KS, Perry D, Kruger R, Qualman S, Barr F, Sorensen P, Triche T, Suijkerbuijk R (Meyer Munroe Institute, University of Nebraska Medical Center, Omaha, NE 68198-3135).

A comparative genomic hybridization (CGH) approach provides identification of genomic gains and losses in a tumor specimen in a single experiment. Only 11 embryonal rhabdomyosarcomas (E-RMS) have been previously subjected to CGH. The underlying genetic events in this histologic subtype are not well defined. In this investigation, 13 E-RMS specimens from 10 patients entered onto IRS I-IV and two local patients were analyzed by CGH and fluorescence in situ hybridization (FISH). Gains of chromosomes or chromosomal regions 2 (62%), 8 (77%), 11q14-22 (69%) and 12q15-21 (62%), and losses of 1p35-36.1 (62%), 6 (54%), 9q13-22 (92%), 16 (77%), 17 (62%), 18 (54%) and 22 (54%) were most prominent. Chromosomal regions 11q14-22 and 9q13-22 represent novel regions of gain and loss, respectively. Importantly, loss of 9q13-22 corresponds with a putative tumor suppressor gene (PTCH) mapped to 9q22 and shown to play a role in rhabdomyosarcoma in a mouse model of Gorlin syndrome¹. Gains of 2, 8 and 12 and loss of 16 were seen in the sole prior E-RMS CGH series²; thus, these data provide important confirmatory results. In contrast to this previous study, however, loss not gain, of chromosomes 17 and 18 were observed in the current study. Chromosome 17 loss correlates well with previous descriptions of frequent allelic loss of 17p (p53) in E-RMS. In summary, CGH and FISH analyses of 13 E-RMS specimens revealed novel genomic imbalances which may be useful in directing further molecular studies for the determination of E-RMS critically involved genes.

1. Hahn, H et al. Nature Med 4:619-622, 1998.
2. Weber-Hall, S et al. Cancer Res 56:3220-3224, 1996.

This work was supported in part by the John A. Wiebe Children’s Health Care Fund, the National Children’s Cancer Foundation and the Orthopaedic Research and Education Foundation.