中国癌症杂志 ›› 2021, Vol. 31 ›› Issue (4): 344-349.doi: 10.19401/j.cnki.1007-3639.2021.04.015

• 综述 • 上一篇    下一篇

同源重组缺陷检测在肿瘤临床诊疗中的研究进展与展望

郁 俐 1 ,沈敏娜 1 ,姜惠琴 1 ,王蓓丽 1,2 ,郭 玮 1,2   

  1. 1. 复旦大学附属中山医院检验科,上海 200032 ;
    2. 复旦大学附属中山医院厦门医院检验科,福建 厦门 361015
  • 出版日期:2021-04-30 发布日期:2021-04-29
  • 通信作者: 郭 玮 E-mail:guo.wei@zs-hospital.sh.ch
  • 基金资助:
    复旦大学附属中山医院青年基金(2020ZSQN34);国家自然科学基金(81772263,81972000,81902139);2019厦门市医疗卫生重点项目(YDZX20193502000002);复旦大学附属中山医院临床研究专项基金 (2018ZSLC05);上海市临床重点专科建设项目(医学检验科)。

The progress and prospect of homologous recombination deficiency detection in clinical diagnosis and treatment of cancer

YU Li 1 , SHEN Minna 1 , JIANG Huiqin 1 , WANG Beili 1,2 , GUO Wei 1,2    

  1. 1. Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; 2. Department of Laboratory Medicine, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen 361015, Fujian Province, China
  • Published:2021-04-30 Online:2021-04-29
  • Contact: GUO Wei E-mail: guo.wei@zs-hospital.sh.ch

摘要: 同源重组(homologous recombination,HR)是修复DNA双链断裂、单链DNA间隙和停滞或折叠复制叉的主要途径,有助于端粒维持,确保减数分裂过程中染色体的正确分离。同源重组修复(homologous recombination repair,HRR)通路是DNA损伤修复通路之一,在肿瘤中有较高的突变频率。除了BRCA1/2基因突变之外,同源重组缺陷(homologous recombination deficiency,HRD)也可以由其他机制引起,例如HRR相关基因的胚系突变、体细胞突变、基因组稳定性及HRR途径中涉及基因的表观遗传修饰等。最新临床研究数据发现,通过HRR基因突变检测和基因瘢痕检测来反映HRD状态可有效预测肿瘤患者使用多腺苷二磷酸核糖聚合酶[poly(ADP-ribose)polymerase,PARP]抑制剂(PARP inhibitor,PARPi)的疗效,帮助患者精准用药及预后判断。鉴于在肿瘤中识别HRD的方法多种多样。总结HRD检测方法,探讨HRD检测在临床实践中的价值,为肿瘤的精准治疗奠定基础。

关键词: 肿瘤, 同源重组缺陷, 多腺苷二磷酸核糖聚合酶抑制剂, 精准治疗

Abstract: Homologous recombination (HR) is the main way to repair DNA double-stranded breaks, single-stranded DNA gaps and stagnation or folding replication forks, helping to maintain telomeres and ensure the correct segregation of chromosomes during meiosis. Homologous recombination repair (HRR) pathway is one of the DNA damage repair pathways, which has a high mutation frequency in cancers. Besides BRCA1/2 mutations, homologous recombination deficiency (HRD) can also be caused by other mechanisms, such as germline mutations, somatic mutations, genome stability of HRR-related genes and epigenetic modification of HRR genes. The latest clinical data show that reflecting HRD status through HRR gene mutations detection and genomic scar detection can effectively predict the efficiency of poly (ADP-ribose) polymerase inhibitor (PARPi) in patients with cancer and help patients to accurately use drugs and predict the prognosis. However, there are a variety of methods to identify HRD in cancers, the purpose of this paper was to summarize the detection methods of homologous recombination, to explore the value of HRD detection in clinical application, and to lay a foundation for precise treatment of cancer.

Key words: Cancer, Homologous recombination deficiency, Poly (ADP-ribose) polymerase inhibitor, Precision therapy