Hsiao Susan J, Black Destin, Devereaux Kelly A, Hagemann Ian S, Jennings Lawrence J, Mandelker Diana, Paulson Vera A, Shiller Michelle, Stockley Tracy L, Vail Eric, Vikas Praveen, Yemelyanova Anna
The Detection of Homologous Recombination Deficiency in Cancer Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Rockville, Maryland; Columbia University Medical Center, New York, New York.
The Detection of Homologous Recombination Deficiency in Cancer Working Group of the Association for Molecular Pathology, Clinical Practice Committee, Rockville, Maryland; Willis-Knighton Medical Center, Shreveport, Louisiana.
J Mol Diagn. 2025 Aug;27(8):685-704. doi: 10.1016/j.jmoldx.2025.05.003. Epub 2025 Jun 13.
Homologous recombination deficiency (HRD) is a genomic feature present in some malignant neoplasms and is attributed to the failure of the homologous recombination repair pathway. Tumors with an HRD-positive status may have a distinct prognosis and/or response to therapies, including poly (ADP-ribose) polymerase inhibitors. The Association for Molecular Pathology assembled an expert panel to examine current practice and perform a scoping review of the medical literature pertaining to the molecular detection of HRD in the clinical setting. The expert panel examined the following topics: components of existing and proposed HRD and genomic instability biomarkers (including mutational signatures, loss of heterozygosity, mutations in homologous recombination repair-associated genes, and epigenetic silencing of RAD51C, BRCA1, or BRCA2); technical considerations for identifying genomic scars from tumor and germline next-generation sequencing results; guidelines on interpretation and caveats when reporting assessments of genomic instability and HRD scores; and the clinical significance of HRD. The panel formulated a set of expert consensus opinion recommendations regarding HRD assay design and validation to guide laboratories in developing HRD tests to ensure high-quality and reproducible results.
同源重组缺陷（HRD）是某些恶性肿瘤中存在的一种基因组特征，归因于同源重组修复途径的功能障碍。HRD阳性状态的肿瘤可能具有独特的预后和/或对包括聚（ADP-核糖）聚合酶抑制剂在内的治疗的反应。分子病理学协会组建了一个专家小组，以审查当前的实践情况，并对临床环境中HRD分子检测的医学文献进行范围界定审查。专家小组审查了以下主题：现有和提议的HRD及基因组不稳定生物标志物的组成部分（包括突变特征、杂合性缺失、同源重组修复相关基因的突变以及RAD51C、BRCA1或BRCA2的表观遗传沉默）；从肿瘤和种系下一代测序结果中识别基因组疤痕的技术考虑因素；报告基因组不稳定和HRD评分评估时的解释指南和注意事项；以及HRD的临床意义。该小组制定了一套关于HRD检测设计和验证的专家共识意见建议，以指导实验室开发HRD检测，确保获得高质量和可重复的结果。
