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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Discovery of structural deletions in breast cancer predisposition genes using whole genome sequencing data from > 2000 women of African-ancestry
Human Genetics, Volume 140, No. 10, Year 2021
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Description
Single germline nucleotide pathogenic variants have been identified in 12 breast cancer predisposition genes, but structural deletions in these genes remain poorly characterized. We conducted in-depth whole genome sequencing (WGS) in genomic DNA samples obtained from 1340 invasive breast cancer cases and 675 controls of African ancestry. We identified 25 deletions in the intragenic regions of ten established breast cancer predisposition genes based on a consensus call from six state-of-the-art SV callers. Overall, no significant case–control difference was found in the frequency of these deletions. However, 1.0% of cases and 0.3% of controls carried any of the eight putative protein-truncating rare deletions located in BRCA1, BRCA2, CDH1, TP53, NF1, RAD51D, RAD51C and CHEK2, resulting in an odds ratio (OR) of 3.29 (95% CI 0.74–30.16). We also identified a low-frequency deletion in NF1 associated with breast cancer risk (OR 1.93, 95% CI 1.14–3.42). In addition, we detected 56 deletions, including six putative protein-truncating deletions, in suspected breast predisposition genes. This is the first large study to systematically search for structural deletions in breast cancer predisposition genes. Many of the deletions, particularly those resulting in protein truncations, are likely to be pathogenic. Results from this study, if confirmed in future large-scale studies, could have significant implications for genetic testing for this common cancer. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Authors & Co-Authors
Guo, Xingyi
United States, Nashville
Vanderbilt University School of Medicine
Long, Jirong
United States, Nashville
Vanderbilt University School of Medicine
Fadden, Mary Kay
United States, Nashville
Meharry Medical College
Ahearn, Thomas U.
United States, Rockville
National Cancer Institute Nci
Stram, Daniel O.
United States, Los Angeles
University of Southern California
Shu, Xiaoou
United States, Nashville
Vanderbilt University School of Medicine
Figueroa, Jonine D.
United Kingdom, Edinburgh
The University of Edinburgh
Adjei, Robertson
Unknown Affiliation
Afriyie, Lucy Twumwaah
Unknown Affiliation
Adjei, Andrew Anthony
Unknown Affiliation
Dedey, Florence
Unknown Affiliation
Vanderpuye, Verna Dnk
Unknown Affiliation
Okyne, Victoria
Unknown Affiliation
Ohene Oti, Naomi O.
Unknown Affiliation
Tay, Evelyn
Unknown Affiliation
Adu-Aryee,
Unknown Affiliation
Kenu, Angela
Unknown Affiliation
Ekpedzor, Obed
Unknown Affiliation
Alcpaloo, Marion
Unknown Affiliation
Boakye, Isaac
Unknown Affiliation
Arhin, Bernard
Unknown Affiliation
Assimah, Emmanuel
Unknown Affiliation
Ka-Chungu, Samuel
Unknown Affiliation
Oppong, Joseph Kwaku
Unknown Affiliation
Osei-Bonsu, Ernest Baawuah
Unknown Affiliation
Frempong, Margaret Agyei
Unknown Affiliation
Brew Abaidoo, Emma
Unknown Affiliation
Amanama, Samuel
Unknown Affiliation
Agyapong, Prince
Unknown Affiliation
Boateng, Debora
Unknown Affiliation
Agyei, Ansong Thomas
Unknown Affiliation
Opoku, Richard
Unknown Affiliation
Brinton, Louise Annette
Unknown Affiliation
Brotzman, Michelle J.
Unknown Affiliation
Niwa, Shelley
Unknown Affiliation
Singh, Usha
Unknown Affiliation
Truelove, Ann L.
Unknown Affiliation
Biritwum, Richard Berko
Unknown Affiliation
Palmer, Julie R.P.
United States, Boston
Boston University
Sanderson, Maureen
United States, Nashville
Meharry Medical College
Haiman, Christopher A.
United States, Los Angeles
University of Southern California
Blot, William J.
United States, Nashville
Vanderbilt University School of Medicine
García-Closas, Montserrat
United States, Rockville
National Cancer Institute Nci
Cai, Qiuyin
United States, Nashville
Vanderbilt University School of Medicine
Zheng, Wei
United States, Nashville
Vanderbilt University School of Medicine
Statistics
Citations: 4
Authors: 45
Affiliations: 7
Identifiers
Doi:
10.1007/s00439-021-02342-8
ISSN:
03406717
Research Areas
Cancer
Genetics And Genomics
Study Design
Case-Control Study
Study Approach
Qualitative
Participants Gender
Female