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<p>African American (AA) women have the highest incidence of triple-negative breast cancer (TNBC) among all ancestral 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 Chinese 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 <i>TP53</i> mutations, low frequency of <i>PIK3CA</i> mutations and mutational signature-based subtypes with etiologic and prognostic significance. These findings do not support major ancestral 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.</p>

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Mutational landscape of triple-negative breast cancer in African American women

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月26日

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  • Song Yao,
  • Lei Wei,
  • Qiang Hu,
  • Song Liu,
  • Zarko Manojlovic,
  • Peter N. Fiorica,
  • Mark Long,
  • Gary R. Zirpoli,
  • Qiuyin Cai,
  • Jirong Long,
  • Jie Ping,
  • Mollie E. Barnard,
  • Yuxin Jin,
  • Mitsuko Murakami,
  • Jianmin Wang,
  • Qianqian Zhu,
  • Warren Davis,
  • Jianhong Chen,
  • Rochelle P. Ondracek,
  • Thaer Khoury,
  • Shipra Gandhi,
  • Kazuaki Takabe,
  • Naomi Ko,
  • Maureen Sanderson,
  • Chi-Chen Hong,
  • Elisa V. Bandera,
  • David W. Craig,
  • Christine B. Ambrosone,
  • Julie R. Palmer,
  • Wei Zheng,
  • John D. Carpten

摘要

African American (AA) women have the highest incidence of triple-negative breast cancer (TNBC) among all ancestral 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 Chinese 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 ancestral 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.