Mutational landscape of triple-negative breast cancer in African American women
African American (AA) women have the highest incidence of triple-negative breast cancer (TNBC) among all racial groups, but are underrepresented in cancer genomic studies. In 462 AA women with TNBC, we characterized the tumor mutational landscape by whole-exome sequencing and RNA sequencing. We unveiled a high-resolution mutational portrait of TNBC in AA women reminiscent of that in Asian and non-Hispanic white women, with no evidence of associations of mutational features with African ancestry. We also made some distinctive discoveries, including an almost complete dominance of TP53 mutations, low frequency of PIK3CA mutations and mutational signature-based subtypes with etiologic and prognostic significance. These findings do not support major racial differences in TNBC biology at the level of somatic mutations. Our study contributes considerably to diversifying the knowledge base of breast cancer genomics and provides insights into the disease etiology, disparities and therapeutic vulnerability of TNBC in AA women.
Authors
- Qiuyin Cai (ORCID: https://orcid.org/0000-0002-9384-5648)
- Maureen Sanderson (ORCID: https://orcid.org/0000-0002-3914-6870)
- Elisa V. Bandera (ORCID: https://orcid.org/0000-0002-8789-2755)
- Chi‐Chen Hong (ORCID: https://orcid.org/0000-0001-9212-2264)
- Mark D. Long (ORCID: https://orcid.org/0000-0003-1120-8176)
- Song Yao (ORCID: https://orcid.org/0000-0001-9442-1313)
- Lei Wei (ORCID: https://orcid.org/0000-0002-1881-8666)
- Christine B. Ambrosone (ORCID: https://orcid.org/0000-0003-1717-9943)
- Peter N. Fiorica (ORCID: https://orcid.org/0000-0002-1001-1518)
- Zarko Manojlovic (ORCID: https://orcid.org/0000-0001-9705-4088)
- Jie Ping (ORCID: https://orcid.org/0000-0001-9907-5819)
- Qiang Hu (ORCID: https://orcid.org/0000-0002-4090-5539)
- Gary Zirpoli (ORCID: https://orcid.org/0000-0003-1417-5349)
- Kazuaki Takabe (ORCID: https://orcid.org/0000-0002-6435-4241)
- Qianqian Zhu (ORCID: https://orcid.org/0000-0003-2516-6675)
- Yuxin Jin (ORCID: https://orcid.org/0000-0002-6124-9681)
- Mollie E. Barnard (ORCID: https://orcid.org/0000-0002-4843-4655)
- Thaer Khoury (ORCID: https://orcid.org/0000-0002-8112-6590)
- Naomi Y. Ko (ORCID: https://orcid.org/0000-0001-9689-9601)
- David W. Craig (ORCID: https://orcid.org/0000-0003-2040-1955)
- Rochelle Payne Ondracek (ORCID: https://orcid.org/0000-0002-4085-3054)
- Mitsuko Murakami (ORCID: https://orcid.org/0000-0002-7476-1254)
- John D. Carpten (ORCID: https://orcid.org/0000-0002-6862-2821)
- Jianmin Wang (ORCID: https://orcid.org/0000-0001-7527-0409)
- Wei Zheng (ORCID: https://orcid.org/0000-0003-1226-070X)
- Jian‐Hong Chen (ORCID: https://orcid.org/0000-0002-9531-0436)
- Jirong Long (ORCID: https://orcid.org/0000-0002-7433-9766)
- Song Liu
- Julie R. Palmer
- W. Davis
- Shipra Gandhi
Institutions
- Rutgers, The State University of New Jersey (US)
- Boston University (US)
- Meharry Medical College (US)
- Boston Medical Center (US)
- Roswell Park Comprehensive Cancer Center (US)
- City of Hope (US)
- Rutgers Cancer Institute (US)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Nature Genetics
- Published
- 2025-08-26
- DOI
- https://doi.org/10.1038/s41588-025-02322-y
- Citations
- 3
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 2.81
Funders
- Breast Cancer Research Foundation
- National Cancer Institute