Ordered and deterministic cancer genome evolution after p53 loss.

ABSTRACT: Although p53 inactivation promotes genomic instability¹ and presents a route to malignancy for more than half of all human cancers^2,3, the patterns through which heterogenous TP53 (encoding human p53) mutant genomes emerge and influence tumorigenesis remain poorly understood. Here, in a mouse model of pancreatic ductal adenocarcinoma that reports sporadic p53 loss of heterozygosity before cancer onset, we find that malignant properties enabled by p53 inactivation are acquired through a predictable pattern of genome evolution. Single-cell sequencing and in situ genotyping of cells from the point of p53 inactivation through progression to frank cancer reveal that this deterministic behaviour involves four sequential phases-Trp53 (encoding mouse p53) loss of heterozygosi

SUBMITTER: Baslan T 

PROVIDER: S-EPMC9402436 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature