Finding significance: New perspectives in variant classification of the RAD51 regulators, BRCA2 and beyond

IF 3 3区生物学 Q2 GENETICS & HEREDITY

DNA Repair Pub Date : 2023-10-01 DOI:10.1016/j.dnarep.2023.103563

Hayley L. Rein , Kara A. Bernstein

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引用次数: 0

Abstract

For many individuals harboring a variant of uncertain functional significance (VUS) in a homologous recombination (HR) gene, their risk of developing breast and ovarian cancer is unknown. Integral to the process of HR are BRCA1 and regulators of the central HR protein, RAD51, including BRCA2, PALB2, RAD51C and RAD51D. Due to advancements in sequencing technology and the continued expansion of cancer screening panels, the number of VUS identified in these genes has risen significantly. Standard practices for variant classification utilize different types of predictive, population, phenotypic, allelic and functional evidence. While variant analysis is improving, there remains a struggle to keep up with demand. Understanding the effects of an HR variant can aid in preventative care and is critical for developing an effective cancer treatment plan. In this review, we discuss current perspectives in the classification of variants in the breast and ovarian cancer genes BRCA1, BRCA2, PALB2, RAD51C and RAD51D.

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发现意义：RAD51调节因子、BRCA2及其他变体分类的新视角。

对于许多在同源重组（HR）基因中携带不确定功能意义变体（VUS）的个体来说，他们患癌症的风险是未知的。参与HR过程的是BRCA1和中枢HR蛋白RAD51的调节因子，包括BRCA2、PALB2、RAD51C和RAD51D。由于测序技术的进步和癌症筛查小组的不断扩大，在这些基因中鉴定的VUS数量显著增加。变异分类的标准实践利用不同类型的预测性、群体性、表型、等位基因和功能性证据。尽管变异分析正在改进，但仍难以满足需求。了解HR变异的影响有助于预防性护理，对于制定有效的癌症治疗计划至关重要。在这篇综述中，我们讨论了乳腺癌和卵巢癌癌症基因BRCA1、BRCA2、PALB2、RAD51C和RAD51D变异分类的最新观点。

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

DNA Repair 生物-毒理学

CiteScore

7.60

自引率

5.30%

发文量

审稿时长

59 days

期刊介绍： DNA Repair provides a forum for the comprehensive coverage of DNA repair and cellular responses to DNA damage. The journal publishes original observations on genetic, cellular, biochemical, structural and molecular aspects of DNA repair, mutagenesis, cell cycle regulation, apoptosis and other biological responses in cells exposed to genomic insult, as well as their relationship to human disease. DNA Repair publishes full-length research articles, brief reports on research, and reviews. The journal welcomes articles describing databases, methods and new technologies supporting research on DNA repair and responses to DNA damage. Letters to the Editor, hot topics and classics in DNA repair, historical reflections, book reviews and meeting reports also will be considered for publication.