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• W2066604004 abstract "The tumor suppressor gene TP53 is the most commonly mutated gene in human cancer. The reported prevalence of mutations in rhabdomyosarcoma (RMS) varies widely, with recent larger studies suggesting that TP53 mutations in pediatric RMS may be extremely rare. Overexpression of MDM2 also attenuates p53 function. We have performed TP53 mutation/ MDM2 amplification 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 (<mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML><mml:mi>N</mml:mi><mml:mo>=</mml:mo><mml:mn>48</mml:mn></mml:math>) and histopathology slides. TP53 mutations in exons 4–9 were analyzed by direct sequencing in all samples, and MDM2 amplification analysis was performed by differential PCR on a subset of 22 samples. We found only one sample (1/75, 1.3%) carrying a TP53 mutation at codon 259 (p.D259Y) and no MDM2 amplification. Two SNPs in the TP53 pathway, associated with accelerated tumor onset in germline TP53 mutation carriers, ( TP53 SNP72 (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 of TP53 mutations/ MDM2 amplifications in pediatric RMS (1.33% and 0%, respectively). The possible inactivation of p53 function by other mechanisms thus remains to be elucidated." @default.
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• W2066604004 date "2012-01-01" @default.
• W2066604004 modified "2023-09-23" @default.
• W2066604004 title "Low Prevalence of<i>TP53</i>Mutations and<i>MDM2</i>Amplifications in Pediatric Rhabdomyosarcoma" @default.
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• W2066604004 doi "https://doi.org/10.1155/2012/492086" @default.
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