Journal article
Rare key functional domain missense substitutions in MRE11A, RAD50, and NBN contribute to breast cancer susceptibility: Results from a Breast Cancer Family Registry case-control mutation-screening study
F Damiola, M Pertesi, J Oliver, F Le Calvez-Kelm, C Voegele, EL Young, N Robinot, N Forey, G Durand, MP Vallée, K Tao, TC Roane, GJ Williams, JL Hopper, MC Southey, IL Andrulis, EM John, DE Goldgar, F Lesueur, SV Tavtigian
Breast Cancer Research | Published : 2014
DOI: 10.1186/bcr3669
Abstract
Introduction: The MRE11A-RAD50-Nibrin (MRN) complex plays several critical roles related to repair of DNA double-strand breaks. Inherited mutations in the three components predispose to genetic instability disorders and the MRN genes have been implicated in breast cancer susceptibility, but the underlying data are not entirely convincing. Here, we address two related questions: (1) are some rare MRN variants intermediate-risk breast cancer susceptibility alleles, and if so (2) do the MRN genes follow a BRCA1/BRCA2 pattern wherein most susceptibility alleles are protein-truncating variants, or do they follow an ATM/CHEK2 pattern wherein half or more of the susceptibility alleles are missense ..
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Awarded by National Institutes of Health
Funding Acknowledgements
This work was supported by the United States National Institutes of Health (NIH) National Cancer Institute (NCI) grant R01 CA121245, by the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer program, by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, and the Ministere de l'enseignement superieur, de la recherche, de la science, et de la technologie du Quebec through Genome Quebec. The BCFR was supported by grant UM1 CA164920 from the NCI. The work also benefited from the Huntsman Cancer Institute's Bioinformatics Shared Resource, which is supported by NCI grant P30 CA042014. The content of this manuscript does not necessarily reflect the views or policies of the NCI or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government or the BCFR.