在美国，非洲裔女性的乳腺癌死亡率最高，并且比其他人群的女性更有可能患上侵袭性疾病。目前尚不清楚非洲乳腺癌在多大程度上与非裔美国人或欧洲裔美国人患者的乳腺癌相似。在这里，我们对来自 97 名非裔美国人、69 名欧洲裔美国人、2 名亚裔美国人和 23 名肯尼亚患者的 191 对乳腺肿瘤和非癌性邻近组织对的基因组 DNA 进行了全外显子组测序。我们对测序数据的分析显示，与欧洲裔美国患者相比，肯尼亚和非裔美国患者的肿瘤突变负担较高。 TP53 突变最常见，特别是在非裔美国人患者中，其次是 PIK3CA 突变，在欧洲裔美国人、非裔美国人和肯尼亚患者中显示出相似的频率。针对 TBX3 的突变仅限于欧洲裔美国人，而针对 FBXW7 肿瘤抑制基因的突变则针对非洲裔美国患者，而已知可赋予内分泌治疗耐药性的 ARID1A 基因突变在肯尼亚患者中明显丰富。 KEGG 通路分析可以将 FBXW7 突变与携带这些突变的肿瘤中线粒体氧化磷酸化能力的增强联系起来。最后，肿瘤中的 COSMIC 突变特征与驱动突变、免疫细胞谱和邻里剥夺的发生相关，其关联范围从大部分适度到偶尔强烈。总之，我们发现这些患者组之间的突变谱不同。差异集中在乳腺癌中突变频率较低的基因中。

Women of African descent have the highest breast cancer mortality in the United States and are more likely than women from other population groups to develop an aggressive disease. It remains uncertain to what extent breast cancer in Africa is reminiscent of breast cancer in African American or European American patients. Here, we performed whole exome sequencing of genomic DNA from 191 breast tumor and non-cancerous adjacent tissue pairs obtained from 97 African American, 69 European American, 2 Asian American, and 23 Kenyan patients. Our analysis of the sequencing data revealed an elevated tumor mutational burden in both Kenyan and African American patients, when compared to European American patients. TP53 mutations were most prevalent, particularly in African American patients, followed by PIK3CA mutations, which showed similar frequencies in European American, African American, and the Kenyan patients. Mutations targeting TBX3 were confined to European Americans and those targeting the FBXW7 tumor suppressor to African American patients whereas mutations in the ARID1A gene that are known to confer resistance to endocrine therapy were distinctively enriched among Kenyan patients. A KEGG pathway analysis could link FBXW7 mutations to an increased mitochondrial oxidative phosphorylation capacity in tumors carrying these mutations. Lastly, COSMIC mutational signatures in tumors correlated with the occurrence of driver mutations, immune cell profiles, and neighborhood deprivation with associations ranging from being mostly modest to occasionally robust. To conclude, we found mutational profiles that were different between these patient groups. The differences concentrated among genes with low mutation frequencies in breast cancer.