Discovery of mutations in homologous recombination genes in African-American women with breast cancer
| Autor: | Gail E. Tomlinson, Yuan Chun Ding, Aaron Adamson, Susan L. Neuhausen, Esther M. John, Adam M. Bailis, Linda Steele |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
0301 basic medicine Cancer Research PALB2 Mutation Missense Breast Neoplasms Gene mutation Biology medicine.disease_cause Article Young Adult 03 medical and health sciences Germline mutation Breast cancer XRCC3 Genetics medicine Humans Genetic Predisposition to Disease Homologous Recombination Germ-Line Mutation Genetics (clinical) Aged Cancer Middle Aged medicine.disease Black or African American DNA-Binding Proteins 030104 developmental biology Oncology RAD51C Female Fanconi Anemia Complementation Group N Protein Carcinogenesis |
| Zdroj: | Familial Cancer. 17:187-195 |
| ISSN: | 1573-7292 1389-9600 |
| DOI: | 10.1007/s10689-017-0036-4 |
| Popis: | African-American women are more likely to develop aggressive breast cancer at younger ages and experience poorer cancer prognoses than non-Hispanic Caucasians. Deficiency in repair of DNA by homologous recombination (HR) is associated with cancer development, suggesting that mutations in genes that affect this process may cause breast cancer. Inherited pathogenic mutations have been identified in genes involved in repairing DNA damage, but few studies have focused on African-Americans. We screened for germline mutations in seven HR repair pathway genes in DNA of 181 African-American women with breast cancer, evaluated the potential effects of identified missense variants using in silico prediction software, and functionally characterized a set of missense variants by yeast two-hybrid assays. We identified five likely-damaging variants, including two PALB2 truncating variants (Q151X and W1038X) and three novel missense variants (RAD51C C135R, and XRCC3 L297P and V337E) that abolish protein-protein interactions in yeast two-hybrid assays. Our results add to evidence that HR gene mutations account for a proportion of the genetic risk for developing breast cancer in African-Americans. Identifying additional mutations that diminish HR may provide a tool for better assessing breast cancer risk and improving approaches for targeted treatment. |
| Databáze: | OpenAIRE |
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