Mutational processes of distinct POLE exonuclease domain mutants drive an enrichment of a specific TP53 mutation in colorectal cancer

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Fang , H , Barbour , J A , Poulos , R C , Katainen , R , Aaltonen , L A & Wong , J W H 2020 , ' Mutational processes of distinct POLE exonuclease domain mutants drive an enrichment of a specific TP53 mutation in colorectal cancer ' , PLoS Genetics , vol. 16 , no. 2 , e1008572 . https://doi.org/10.1371/journal.pgen.1008572

Title: Mutational processes of distinct POLE exonuclease domain mutants drive an enrichment of a specific TP53 mutation in colorectal cancer
Author: Fang, Hu; Barbour, Jayne A.; Poulos, Rebecca C.; Katainen, Riku; Aaltonen, Lauri A.; Wong, Jason W. H.
Contributor: University of Helsinki, ATG - Applied Tumor Genomics
University of Helsinki, Genome-Scale Biology (GSB) Research Program
Date: 2020-02-03
Number of pages: 20
Belongs to series: PLoS Genetics
ISSN: 1553-7390
URI: http://hdl.handle.net/10138/313635
Abstract: Author summary Cancer arises through the accumulation of somatic mutations. The way that these somatic mutations form can vary greatly in different cancers. One of the most mutagenic processes that have been identified is caused by mutations within a replicative DNA polymerase known as Polymerase Epsilon (POLE). Cancers with such mutations present with hundreds of thousands of somatic mutations in their genome. Previous cancer genomics studies have identified a number of mutation hotspots in POLE, however how these different POLE mutants behave in affecting mutation distribution has not been studied. Here, we describe the genome-wide mutation profiles of distinct POLE mutant cancers. We find that different mutants indeed result in different mutation profiles and that this can be explained by the different fidelities of these mutants in replicating specific DNA sequences. Significantly, these differences have important implications in cancer formation as we found that a POLE mutation is strongly associated with a specific truncation of the TP53 cancer driver gene. This study furthers our understanding of the POLE mutagenic process in cancer and provide important insights into carcinogenesis in cancers with such mutations.
Subject: 3111 Biomedicine
1184 Genetics, developmental biology, physiology
3122 Cancers
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