MOLECULAR CHARACTERIZATION OF SOLID PEDIATRIC TUMORS

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(a)Rhabdomyosarcoma (RMS)-alveolar versus embryonal: A consistent t(2;13)(q35;q14) translocation in alveolar RMS results in fusion between PAX3 or PAX7 genes with the FKHR factors. Using reverse transcription (RT)-PCR and fluorescence in situ hybridization (FISH) technique, we will investigate the presence of PAX3 (PAX7)/FKHR transcripts in a large number of alveolar RMS. Embryonal RMS on the other hand exhibits a reproducible loss of chromosomal material on chromosome 11p15.5. We plan to use RFLP and appropriate chromosomal probes to investigate the frequency by which loss of heterozygosity (LOH) of locus 11p15.5 is encountered in human embryonal RMS. (b)Neuroectodermal tumors: The reciprocal t(11;22)(q24;q12) and t(21;22) (q22;q12) translocations in the family of peripheral neuroectodermal tumors (PNET) result in fusion between the EWS gene in chromosome 22 and the Fli1 or erg genes in chromosomes 11 and 21 respectively generating fusion transcripts detectable by RT-PCR. We have currently analyzed 50 tumors with a presumable diagnosis of Ewing's a sarcoma/PNET for the presence of these transcripts by RT-PCR. The neurofibromatosis (NF)1 gene which is considered to be a possible tumor suppressor gene has been mapped to chromosome band 17q11.2. LOH of the NF1 locus has been reported in a malignant nerve sheath tumor but not in benign neurofibromas from a patient with NF 1. In addition, loss of regions on chromosome 22 (q11.3-12) which harbors the NF2 gene have been reported in tumors from a NF1 patient. We will undertake LOH studies for chromosomes 17, 11 and 22 in benign and malignant neuroectodermal tumors (nerve sheath and PNET) occurring sporadically and in patients with NF to evaluate possible molecular differences.