University of Pittsburgh, School of Medicine, Department of Pharmacology and Chemical Biology, Pittsburgh, PA, USA.
University of Pennsylvania School of Medicine, Department of Biochemistry and Biophysics, 421 Curie Boulevard, Philadelphia, PA, USA.
DNA Repair (Amst). 2023 Oct;130:103563. doi: 10.1016/j.dnarep.2023.103563. Epub 2023 Aug 19.
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.
对于许多携带有同源重组（HR）基因不确定功能意义变异（VUS）的个体，其患乳腺癌和卵巢癌的风险尚不清楚。BRCA1 和 HR 蛋白中央调节剂 RAD51 的调控因子，包括 BRCA2、PALB2、RAD51C 和 RAD51D，是 HR 过程的重要组成部分。由于测序技术的进步和癌症筛查面板的不断扩展，这些基因中 VUS 的数量显著增加。用于变异分类的标准实践利用不同类型的预测、人群、表型、等位和功能证据。虽然变异分析在不断改进，但仍然难以满足需求。了解 HR 变异的影响有助于进行预防保健，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基因 BRCA1、BRCA2、PALB2、RAD51C 和 RAD51D 中变异分类的当前观点。
