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分析阿拉伯裔本土乳腺癌患者中的药物基因组学变异。

Profiling of pharmacogenomic variants in and in indigenous Arab breast cancer patients.

机构信息

College of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia.

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

出版信息

Pharmacogenomics. 2023 May;24(7):411-423. doi: 10.2217/pgs-2023-0029. Epub 2023 May 24.

Abstract

The indigenous Arab population is underrepresented in genomic studies and the landscape of actionable pharmacogenomic variants among Arab breast cancer patients remains unclear. Exome sequencing was performed on 220 unselected Arab female breast cancer patients and germline variants in and were profiled using a deep learning method. In total, 13 (5.9%) patients had clinically actionable results and 56 (25.5%) carried an allele in or with unknown impact on drug metabolism. In addition, four unique novel missense variants were discovered, including one in  (p.Arg64Leu) with high predicted pathogenicity. A nontrivial subset of Arab breast cancer patients can potentially benefit from pretreatment molecular profiling, and further study is needed to improve characterization of the pharmacogenomic landscape.

摘要

在基因组研究中,本土阿拉伯人群代表性不足,阿拉伯裔乳腺癌患者可操作的药物基因组学变异的情况仍不清楚。对 220 名未经选择的阿拉伯裔女性乳腺癌患者进行了外显子组测序,并使用深度学习方法对 和 中的种系变异进行了分析。共有 13 名(5.9%)患者有临床可操作的结果,56 名(25.5%)患者携带 或 中对药物代谢有未知影响的等位基因。此外,还发现了四个独特的新错义变异,包括一个在 (p.Arg64Leu)中具有高预测致病性的变异。有相当一部分阿拉伯裔乳腺癌患者可能从预处理分子谱中受益,需要进一步研究以改善对药物基因组学图谱的描述。

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