Low Prevalence ofTP53Mutations andMDM2Amplifications in Pediatric Rhabdomyosarcoma

The tumor suppressor geneTP53is the most commonly mutated gene in human cancer. The reported prevalence of mutations in rhabdomyosarcoma (RMS) varies widely, with recent larger studies suggesting thatTP53mutations in pediatric RMS may be extremely rare. Overexpression of MDM2 also attenuates p53 function. We have performedTP53mutation/MDM2amplification analyses in the largest series analyzed thus far, including DNA isolated from 37 alveolar and 38 embryonal RMS tumor samples obtained from the Cooperative Human Tissue Network (CHTN). Available samples were frozen tumor tissues (N=48) and histopathology slides.TP53mutations in exons 4–9 were analyzed by direct sequencing in all samples, andMDM2amplification analysis was performed by differential PCR on a subset of 22 samples. We found only one sample (1/75, 1.3%) carrying aTP53mutation at codon 259 (p.D259Y) and noMDM2amplification. Two SNPs in theTP53pathway, associated with accelerated tumor onset in germlineTP53mutation carriers, (TP53SNP72 (rs no. 1042522) and MDM2 SNP309 (rs no. 2279744)), were not found to confer earlier tumor onset. In conclusion, we confirm the extremely low prevalence ofTP53mutations/MDM2amplifications in pediatric RMS (1.33% and 0%, respectively). The possible inactivation of p53 function by other mechanisms thus remains to be elucidated.