Dutta Pranabananda, Keung Man Y, Wu Yanyuan, Vadgama Jaydutt V
Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA.
David Geffen UCLA School of Medicine, Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Oncol Lett. 2022 Dec 16;25(2):51. doi: 10.3892/ol.2022.13637. eCollection 2023 Feb.
Breast cancer is a disease with significant health disparity affecting mortality in minority women. The present study examined the genetic makeup of breast cancers in African-American and Hispanic/Latinx patients to determine specific genetic mutations associated with breast cancer in the minority population from South Los Angeles, United States. Whole-exome sequencing was performed on DNA extracted from breast cancer tumor biopsies collected from 13 African-American and 15 Hispanic women and 8 matched-normal samples for each ethnic category. The results were analyzed using Ensemble Variant Effect Predictor and Mutation Significance. Additionally, a comparative analysis with The Cancer Genome Atlas data was provided. Our data revealed somatic mutations in genes such as SET domain containing (lysine methyltransferase) 8, serine protease 1 and AT-rich interaction domain 1B () and known breast cancer genes, such as and the DNA damage response genes across all ethnicities. Additionally, Hispanic patients had BRCA1 associated RING domain 1B () variants, while African-American patients had higher numbers of nonsynonymous variants in the RAD51 paralog B (), and X-ray repair cross complementing 3 () genes. In addition, our patients exhibited mutational signature enrichment that indicated DNA homologous recombination repair deficiencies. Therefore, African-American and Hispanic breast cancer samples showed considerable overlap in breast cancer genetic mutations. However, there are differences in specific genetic variants in or , which will require further study of their role in tumorigenesis.
乳腺癌是一种存在显著健康差异、影响少数族裔女性死亡率的疾病。本研究检测了非裔美国人和西班牙裔/拉丁裔患者乳腺癌的基因组成，以确定与美国南洛杉矶少数族裔人群乳腺癌相关的特定基因突变。对从13名非裔美国女性和15名西班牙裔女性的乳腺癌肿瘤活检组织以及每个种族类别的8个匹配正常样本中提取的DNA进行了全外显子测序。使用Ensemble变异效应预测器和突变显著性对结果进行分析。此外，还提供了与癌症基因组图谱数据的比较分析。我们的数据揭示了所有种族中含SET结构域（赖氨酸甲基转移酶）8、丝氨酸蛋白酶1和富含AT相互作用结构域1B（）等基因以及已知乳腺癌基因如和DNA损伤反应基因中的体细胞突变。此外，西班牙裔患者有BRCA1相关的RING结构域1B（）变异，而非裔美国患者在RAD51旁系同源物B（）、和X射线修复交叉互补3（）基因中有更多的非同义变异。此外，我们的患者表现出突变特征富集，表明DNA同源重组修复缺陷。因此，非裔美国人和西班牙裔乳腺癌样本在乳腺癌基因突变方面有相当大的重叠。然而，在或中的特定基因变异存在差异，这将需要进一步研究它们在肿瘤发生中的作用。
