Association between ancestry and tumor somatic mutations in a large national cohort of women with breast cancer
Somatic mutations and copy number alterations in breast tumors are important to determine prognosis, predict treatment response, and identify targets for therapy. We utilized somatic sequencing data of breast tumors from Foundation Medicine Inc. to evaluate the association between genetic ancestry and somatic mutations. We used germline variants to infer genetic ancestry with both principal components analysis and ADMIXTURE. Overall, we identified 91 ancestry-specific somatic differences across 58 unique genes, which included potentially targetable genes such as PIK3CA found in higher frequency in European ancestry, and EGFR found in higher frequency in East Asian ancestry. Pan-cancer analysis of East Asian ancestry and EGFR also found higher frequency in prostate, thyroid, and kidney cancers. African ancestry was associated with increased frequency of copy number alterations overall and decreased frequency of multiple genes on the PI3K-AKT pathway. Future research is warranted to elicit the genetic and environmental conditions that underly these findings.
Authors
- Kirkpatrick B. Fergus (ORCID: https://orcid.org/0000-0002-3559-1109)
- Ray Greenstein
- Luis G. Carvajal‐Carmona (ORCID: https://orcid.org/0000-0001-7129-2918)
- Justin Y. Newberg (ORCID: https://orcid.org/0000-0002-3764-4956)
- Niharika Dixit (ORCID: https://orcid.org/0000-0001-6954-2383)
- Elad Ziv (ORCID: https://orcid.org/0000-0002-2324-2884)
- Garrett M. Frampton (ORCID: https://orcid.org/0000-0002-2361-2750)
- Laura Fejerman (ORCID: https://orcid.org/0000-0003-3179-1151)
- Franklin W. Huang (ORCID: https://orcid.org/0000-0001-5447-0436)
- Eric A. Collisson (ORCID: https://orcid.org/0000-0002-2829-355X)
- Susan L. Neuhausen
Institutions
- San Francisco General Hospital (US)
- San Francisco VA Medical Center (US)
- Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA)
- Cancer Research Institute (US)
- University of California, San Francisco (US)
- Boston Foundation (US)
- Fred Hutch Cancer Center (US)
- City of Hope (US)
- Institute of Human Genetics (PL)
- Chan Zuckerberg Initiative (United States) (US)
- UCSF Helen Diller Family Comprehensive Cancer Center (US)
- Beckman Research Institute
- Foundation Medicine (United States)
- University of California, Davis (US)
Publication Details
- Journal
- npj Breast Cancer
- Published
- 2025-10-29
- DOI
- https://doi.org/10.1038/s41523-025-00815-x
- Citations
- 1
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- Conquer Cancer Foundation
- National Institutes of Health
- Foundation Medicine
- National Cancer Institute