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Effect of the p53 P72R Polymorphism on Mutant TP53 Allele Selection in Human Cancer by Cristabelle De Souza; Jill Madden; Devin C Koestler; Dennis Minn; Dennis J Montoya; Kay Minn; Alan G Raetz; Zheng Zhu; Wen-Wu Xiao; Neeki Tahmassebi; Harikumara Reddy; Nina Nelson; Anthony N Karnezis; Jeremy Chien is a Medicine article available to read on EtoBox.

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## Abstract ## Background TP53 mutations occur in more than 50% of cancers. We sought to determine the effect of the intragenic P72R single nucleotide polymorphism (SNP; rs1042522) on the oncogenic properties of mutant p53. ## Methods P72R allelic selection in tumors was determined from genotype calls and a Gaussian distributed mixture model. The SNP effect on mutant p53 was determined in p53-negative cancer cell lines. RNA-sequencing, chromatin immunoprecipitation, and survival analysis were performed to describe the SNP effect. All statistical tests were 2-sided. ## Results Among 409 patients with germline heterozygous P72R SNP who harbored somatic mutations in TP53, we observed a selection bias against missense TP53 mutants encoding the P72 SNP (P = 1.64 x 10-13). Exogenously expressed hotspot p53 mutants with the P72 SNP were negatively selected in cancer cells. Gene expression analyses showed the enrichment of p53 pathway genes and inflammatory genes in cancer cells transduced with mutants encoding P72 SNP. Immune gene signature is enriched in patients harboring missense TP53 mutations with homozygous P72 SNP. These patients have improved overall survival as compared with thos

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Author

Cristabelle De Souza; Jill Madden; Devin C Koestler; Dennis Minn; Dennis J Montoya; Kay Minn; Alan G Raetz; Zheng Zhu; Wen-Wu Xiao; Neeki Tahmassebi; Harikumara Reddy; Nina Nelson; Anthony N Karnezis; Jeremy Chien

Publisher

Oxford University Press (OUP)

Published

2021

Language

EN

Field

Medicine (Health Sciences)