同源重组缺陷（HRD）导致了有缺陷的双链断裂修复，是肿瘤发生的普遍原因。然而，在泛癌症患者中，HRD的发生率及其临床意义仍然未知。通过对10,619名癌症患者的单核苷酸多态性芯片数据进行计算分析，我们表明HRD在多种癌症类型中经常发生。泛癌症队列的分析揭示了HRD不仅是卵巢癌和三阴性乳腺癌的生物标志物，而且在许多癌症类型中具有临床预后价值，包括肾上腺皮质癌和胸腺瘤。我们发现同源重组相关基因具有高突变或删除频率。通路分析显示HRD与DNA损伤响应和免疫相关信号通路呈正相关。肿瘤浸润淋巴细胞的单细胞RNA测序显示，在HRD患者中，疲惫的T细胞比例显著更高，表明了既往存在的免疫性。最后，HRD可以用于预测泛癌症患者对程序性细胞死亡蛋白1免疫疗法的反应。总之，我们的工作建立了一张泛癌症的HRD综合地图。这些发现对于扩大Poly ADP核糖合酶抑制剂治疗的范围以及可能的免疫疗法具有重要意义。©2023. 作者（S）。

Homologous recombination deficiency (HRD) causes faulty double-strand break repair and is a prevalent cause of tumorigenesis. However, the incidence of HRD and its clinical significance in pan-cancer patients remain unknown. Using computational analysis of Single-nucleotide polymorphism array data from 10,619 cancer patients, we demonstrate that HRD frequently occurs across multiple cancer types. Analysis of the pan-cancer cohort revealed that HRD is not only a biomarker for ovarian cancer and triple-negative breast cancer, but also has clinical prognostic value in numerous cancer types, including adrenocortical cancer and thymoma. We discovered that homologous recombination-related genes have a high mutation or deletion frequency. Pathway analysis shows HRD is positively correlated with the DNA damage response and the immune-related signaling pathways. Single cell RNA sequencing of tumor-infiltrating lymphocytes reveals a significantly higher proportion of exhausted T cells in HRD patients, indicating pre-existing immunity. Finally, HRD could be utilized to predict pan-cancer patients' responses to Programmed cell death protein 1 immunotherapy. In summary, our work establishes a comprehensive map of HRD in pan-cancer. The findings have significant implications for expanding the scope of Poly ADP-ribose polymerase inhibitor therapy and, possibly, immunotherapy.© 2023. The Author(s).