Yao Song, Wei Lei, Hu Qiang, Liu Song, Manojlovic Zarko, Fiorica Peter N, Long Mark, Zirpoli Gary R, Cai Qiuyin, Long Jirong, Ping Jie, Barnard Mollie E, Jin Yuxin, Murakami Mitsuko, Wang Jianmin, Zhu Qianqian, Davis Warren, Chen Jianhong, Ondracek Rochelle P, Khoury Thaer, Gandhi Shipra, Takabe Kazuaki, Ko Naomi, Sanderson Maureen, Hong Chi-Chen, Bandera Elisa V, Craig David W, Ambrosone Christine B, Palmer Julie R, Zheng Wei, Carpten John D
Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Nat Genet. 2025 Aug 26. doi: 10.1038/s41588-025-02322-y.
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.
在所有种族群体中，非裔美国（AA）女性的三阴性乳腺癌（TNBC）发病率最高，但在癌症基因组研究中的代表性不足。在462名患有TNBC的AA女性中，我们通过全外显子组测序和RNA测序对肿瘤突变图谱进行了表征。我们揭示了AA女性TNBC的高分辨率突变特征，这与亚洲和非西班牙裔白人女性的情况相似，没有证据表明突变特征与非洲血统有关。我们还取得了一些独特的发现，包括TP53突变几乎完全占主导地位、PIK3CA突变频率较低以及具有病因学和预后意义的基于突变特征的亚型。这些发现不支持在体细胞突变水平上TNBC生物学存在主要种族差异。我们的研究为丰富乳腺癌基因组学的知识库做出了重要贡献，并为AA女性TNBC的疾病病因、差异和治疗易感性提供了见解。
