Common genetic variants in the TP53 pathway and their impact on cancer

作     者：Thibaut Barnoud Joshua L.D.Parris Maureen E.Murphy Thibaut Barnoud;Joshua L.D.Parris;Maureen E.Murphy

作者机构：Program in Molecular and Cellular OncogenesisThe Wistar InstitutePhiladelphiaPA 19104USA Cell and Molecular Biology ProgramPerelman School of Medicine at the University of PennsylvaniaPhiladelphiaPA 19104USA 

出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)

年 卷 期：2019年第11卷第7期

页      面：578-585页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 09[农学] 

基　　金：supported by the National Institutes of Health 

主　　题：p53 Pro47Ser Pro72Arg PAS MDM2 SNP309 

摘      要：The TP53 gene is well known to be the most frequently mutated gene in human *** addition to mutations,there are 20 different coding region single-nucleotide polymorphisms (SNPs) in the TP53 gene,as well as SNPs in MDM2,the negative regulator of *** of these SNPs are known to alter p53 pathway *** makes p53 rather unique among cancer-critical genes,*** coding regions of other cancer-critical genes like Ha-Ras,RB,and PI3KCA do not have non-synonymous coding region SNPs that alter their function in *** next frontier in p53 biology will consist of probing which of these coding region SNPs are moderately or strongly pathogenic and whether they influence cancer risk and the efficacy of cancer *** challenge after that will consist of determining whether we can tailor chemotherapy to correct the defects for each ofthese *** we review the SNPs in TP53 and MDM2 that show the most significant impact on cancer and other *** also propose avenues for how this information can be used to better inform personalized medicine approaches to cancer and other diseases.