Common polymorphisms in TP53 and MDM2 and the relationship to TP53 mutations and clinical outcomes in women with ovarian and peritoneal carcinomas

✍ Scribed by Vijaya Galic; Julia Willner; Melissa Wollan; Ruchi Garg; Rochelle Garcia; Barbara A. Goff; Heidi J. Gray; Elizabeth M. Swisher

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 202 KB
• Volume: 46
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/gcc.20407

✦ Synopsis

Abstract

The importance of somatic TP53 mutations and germline TP53 codon 72 genotype in the survival of women with epithelial ovarian cancer is controversial. Recent data suggest that a promoter polymorphism in the MDM2 gene may influence age of cancer onset in a gender‐specific fashion. We sought to determine the relationship between somatic TP53 mutations, germline genotypes at TP53 codon 72 and MDM2 SNP309, and overall survival and response to chemotherapy in a large series of patients with ovarian and peritoneal carcinomas. Of the 188 cancers, 103 (54.8%) had a TP53 mutation, of which 71% were missense mutations and 29% were null mutations. TP53 mutation status and mutation type (null vs. missense) did not influence response to therapy or overall survival. Women with the codon 72 Pro/Pro had a decreased overall survival (median, 29 months) compared with women with one or two arginine alleles (median, 49 months; P = 0.04). Somatic mutation or deletion was equally common for either codon 72 allele. Age of diagnosis was not influenced by codon 72 but showed a trend for younger age in women with somatic TP53 mutations and the MDM2 G/G genotype. © 2006 Wiley‐Liss, Inc.