@article{609b9728027e445390a1795233f5a040,
title = "Prospectively defined patterns of APOBEC3A mutagenesis are prevalent in human cancers",
abstract = "Mutational signatures defined by single base substitution (SBS) patterns in cancer have elucidated potential mutagenic processes that contribute to malignancy. Two prevalent mutational patterns in human cancers are attributed to the APOBEC3 cytidine deaminase enzymes. Among the seven human APOBEC3 proteins, APOBEC3A is a potent deaminase and proposed driver of cancer mutagenesis. In this study, we prospectively examine genome-wide aberrations by expressing human APOBEC3A in avian DT40 cells. From whole-genome sequencing, we detect hundreds to thousands of base substitutions per genome. The APOBEC3A signature includes widespread cytidine mutations and a unique insertion-deletion (indel) signature consisting largely of cytidine deletions. This multi-dimensional APOBEC3A signature is prevalent in human cancer genomes. Our data further reveal replication-associated mutations, the rate of stem-loop and clustered mutations, and deamination of methylated cytidines. This comprehensive signature of APOBEC3A mutagenesis is a tool for future studies and a potential biomarker for APOBEC3 activity in cancer.",
keywords = "APOBEC3, CP:Cancer, cancer genome, cytidine deaminase, indel, methylcytidine, mutagenesis, mutational signature",
author = "DeWeerd, {Rachel A.} and Eszter N{\'e}meth and {\'A}d{\'a}m P{\'o}ti and Nataliya Petryk and Chen, {Chun Long} and Olivier Hyrien and D{\'a}vid Sz{\"u}ts and Green, {Abby M.}",
note = "Funding Information: The authors thank all members of the Green and Sz{\"u}ts labs for critical evaluation of experimental data and thoughtful review of the manuscript. We are thankful to colleagues and collaborators for experimental discussions and manuscript editing, especially Drs. Matthew Weitzman, Rahul Kohli, Sebastien Landry, Jeffrey Bednarski, and members of the Bednarski lab. We acknowledge the high-throughput sequencing facility of I2BC for its sequencing and bioinformatics expertise. BioRender was used to generate schematic figures and the graphical abstract. This work was supported by funding from the American Cancer Society (to A.M.G.), the Cancer Research Foundation (to A.M.G.), the National Institutes of Health ( K08 CA212299 to A.M.G.), the Department of Defense ( CA200867 to A.M.G.), the Children's Discovery Institute and the Washington University School of Medicine (to A.M.G.), and the National Research Development and Innovation Office of Hungary ( K_134779 and VEKOP-2.3.3-15-2017-00014 to D.S. and PD_134818 to E.N.). The C.-L.C. lab is supported by the YPI program of I. Curie, the ATIP-Avenir program from Centre National de la Recherche Scientifique and Plan Cancer ( N°18CT014-00 ), the Agence Nationale de la Recherche ( ReDeFINe 19-CE12-0016-02 ), and Institut National Du Cancer ( PLBIO19-076 ). The O.H. lab is supported by Ligue Nationale Contre le Cancer (Comit{\'e} de Paris), Agence Nationale de la Recherche ( ANR 2010 BLAN 161501 ), Association pour la Recherche sur le Cancer , the Fondation pour la Recherche M{\'e}dicale ( FRM DEI201512344404 ), and the France G{\'e}nomique national infrastructure “Investissements d{\textquoteright}Avenir” program managed by the ANR (ANR-10-INBS-09). Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = mar,
day = "22",
doi = "10.1016/j.celrep.2022.110555",
language = "English",
volume = "38",
journal = "Cell Reports",
issn = "2211-1247",
number = "12",
}