van der Wiel Alexander M A, Schuitmaker Lesley, Cong Ying, Theys Jan, Van Hoeck Arne, Vens Conchita, Lambin Philippe, Yaromina Ala, Dubois Ludwig J
The M-Lab, Department of Precision Medicine, GROW-School for Oncology and Reproduction, Maastricht University, 6229 ER Maastricht, The Netherlands.
Center for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.
Cancers (Basel). 2022 Aug 27;14(17):4157. doi: 10.3390/cancers14174157.
Homologous recombination deficiency (HRD) is a prevalent in approximately 17% of tumors and is associated with enhanced sensitivity to anticancer therapies inducing double-strand DNA breaks. Accurate detection of HRD would therefore allow improved patient selection and outcome of conventional and targeted anticancer therapies. However, current clinical assessment of HRD mainly relies on determining germline mutational status and is insufficient for adequate patient stratification as mechanisms of HRD occurrence extend beyond functional BRCA1/2 loss. HRD, regardless of status, is associated with specific forms of genomic and mutational signatures termed HRD scar. Detection of this HRD scar might therefore be a more reliable biomarker for HRD. This review discusses and compares different methods of assessing HRD and HRD scar, their advances into the clinic, and their potential implications for precision oncology.
同源重组缺陷(HRD)在大约17%的肿瘤中普遍存在,并且与对诱导双链DNA断裂的抗癌疗法的敏感性增强相关。因此,准确检测HRD将有助于改善患者选择以及传统和靶向抗癌疗法的疗效。然而,目前HRD的临床评估主要依赖于确定种系突变状态,由于HRD发生机制超出了功能性BRCA1/2缺失的范围,因此不足以进行充分的患者分层。无论状态如何,HRD都与称为HRD疤痕的特定形式的基因组和突变特征相关。因此,检测这种HRD疤痕可能是HRD更可靠的生物标志物。本综述讨论并比较了评估HRD和HRD疤痕的不同方法、它们在临床中的进展以及它们对精准肿瘤学的潜在影响。