Synapse - The landscape of somatic genetic alterations in breast cancers from ATM germline mutation carriers

The landscape of somatic genetic alterations in breast cancers from ATM germline mutation carriers Journal Article

Authors:	Weigelt, B.; Bi, R.; Kumar, R.; Blecua, P.; Mandelker, D. L.; Geyer, F. C.; Pareja, F.; James, P. A.; for the kConFab Investigators; Couch, F. J.; Eccles, D. M.; Blows, F.; Pharoah, P.; Li, A.; Selenica, P.; Lim, R. S.; Jayakumaran, G.; Waddell, N.; Shen, R.; Norton, L.; Wen, H. Y.; Powell, S. N.; Riaz, N.; Robson, M. E.; Reis-Filho, J. S.; Chenevix-Trench, G.
Article Title:	The landscape of somatic genetic alterations in breast cancers from ATM germline mutation carriers
Abstract:	Pathogenic germline variants in ataxia-telangiectasia mutated (ATM), a gene that plays a role in DNA damage response and cell cycle checkpoints, confer an increased breast cancer (BC) risk. Here, we investigated the phenotypic characteristics and landscape of somatic genetic alterations in 24 BCs fromATM germlinemutation carriers by whole-exome and targeted sequencing. ATMassociated BCs were consistently hormone receptor positive and largely displayedminimal immune infiltrate. Although 79.2% of these tumors exhibited loss of heterozygosity of the ATM wild-type allele, none displayed high activity ofmutational signature 3 associated with defective homologous recombination DNA (HRD) repair. No TP53mutations were found in the ATM-associated BCs. Analysis of an independent data set confirmed that germline ATMvariants and TP53 somaticmutations aremutually exclusive. Our findings indicate that ATM-associated BCs often harbor bi-allelic inactivation of ATM, are phenotypically distinct from BRCA1/2-associated BCs, lack HRD-relatedmutational signatures, and that TP53 and ATM genetic alterations are likely epistatic. © 2018 Oxford University Press. All rights reserved.
Journal Title:	JNCI: Journal of the National Cancer Institute
Volume:	110
Issue:	9
ISSN:	0027-8874
Publisher:	Oxford University Press
Date Published:	2018-09-01
Start Page:	1030
End Page:	1034
Language:	English
DOI:	10.1093/jnci/djy028
PROVIDER:	scopus
PMCID:	PMC6136925
PUBMED:	29506079
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85054066794&doi=10.1093%2fjnci%2fdjy028&partnerID=40&md5=a1c47ce049e959b1d1f3e97f160f7011
Notes:	Article -- Export Date: 1 November 2018 -- Source: Scopus