Profiling of pharmacogenomic variants in CYP2D6 and DPYD in indigenous Arab breast cancer patients.

IF 1.9 4区医学 Q3 PHARMACOLOGY & PHARMACY

Pharmacogenomics Pub Date : 2023-05-01 DOI:10.2217/pgs-2023-0029

Abdullah Alsulaiman, Hoyin Chu, Mohammed Al-Jumaan, Mohammed Alyahya, Yousef Al Marzooq, Fatmah Almulhim, Chittibabu Vatte, Areej Alnimer, Afnan Almuhanna, Amein Al-Ali, Saud H AlDubayan

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引用次数: 0

Abstract

Aim: The indigenous Arab population is underrepresented in genomic studies and the landscape of actionable pharmacogenomic variants among Arab breast cancer patients remains unclear. Materials & methods: Exome sequencing was performed on 220 unselected Arab female breast cancer patients and germline variants in CYP2D6 and DPYD were profiled using a deep learning method. Results: In total, 13 (5.9%) patients had clinically actionable results and 56 (25.5%) carried an allele in DYPD or CYP2D6 with unknown impact on drug metabolism. In addition, four unique novel missense variants were discovered, including one in CYP2D6 (p.Arg64Leu) with high predicted pathogenicity. Conclusion: 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.

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土著阿拉伯乳腺癌患者CYP2D6和DPYD的药物基因组变异分析。

目的:土著阿拉伯人口在基因组研究中代表性不足，阿拉伯乳腺癌患者中可操作的药物基因组变异的前景仍不清楚。材料与方法:对220例未选择的阿拉伯女性乳腺癌患者进行外显子组测序，并使用深度学习方法分析CYP2D6和DPYD的种系变异。结果:共有13例(5.9%)患者具有临床可操作的结果，56例(25.5%)患者携带对药物代谢影响未知的DYPD或CYP2D6等位基因。此外，还发现了四个独特的新型错义变异，其中包括CYP2D6中的一个(p.a g64leu)，具有高预测致病性。结论:阿拉伯乳腺癌患者的一个重要亚群可能从预处理分子谱分析中获益，需要进一步的研究来改善药物基因组学景观的表征。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacogenomics 医学-药学

CiteScore

3.40

自引率

9.50%

发文量

审稿时长

4-8 weeks

期刊介绍： Pharmacogenomics (ISSN 1462-2416) is a peer-reviewed journal presenting reviews and reports by the researchers and decision-makers closely involved in this rapidly developing area. Key objectives are to provide the community with an essential resource for keeping abreast of the latest developments in all areas of this exciting field. Pharmacogenomics is the leading source of commentary and analysis, bringing you the highest quality expert analyses from corporate and academic opinion leaders in the field.