云南地区卵巢癌患者的基因同源重组缺陷状态和BRCA1/2基因突变频率及其临床意义

The status of homologous recombination deficiency and BRCA1/2 gene mutation in ovarian cancer patients in the Yunnan region and their clinical significance

目的:采用基于中国人群单核苷酸多态性位点开发的同源重组缺陷(HRD)检测工具评估云南地区卵巢癌患者的HRD状态和BRCA1/2基因突变频率并探讨其临床意义。方法:共纳入2021年1月至2023年5月间在云南省肿瘤医院收治的卵巢癌患者248例,HRD状态采用基因组瘢痕评分法(GSS)(主要依据拷贝数的长度、类型、位置及基因组断片)或HRD评分法(杂合性缺失、端粒等位基因失衡及大片段移位等基因组不稳定事件的总和)进行评估,当组织样本的GSS≥50分或HRD评分≥42分者或检测到有害的BRCA1/2基因突变时HRD被定义为阳性。分析患者HRD状态与临床病理特征的关系。结果:248名卵巢癌患者中70.97%的患者HRD呈阳性,其中BRCA1/2基因突变率为30.65%。Ⅲ~Ⅵ期、高级别浆液腺癌的卵巢癌患者具有更高的HRD阳性率(均P<0.01),HRD评分更高的患者其合并其他基因突变的频率也越高(P<0.05)。HRD状态与卵巢癌的病理类型、临床分期和其他基因突变均有关联(均P<0.01)。结论:云南地区卵巢癌患者HRD阳性率较高,HRD阳性的卵巢癌患者可以从聚ADP核糖聚合酶(PARP)抑制剂治疗中获得更大的收益。

Objective:To evaluate the HRD(homologous recombination deficiency)status of ovarian cancer patients in the Yunnan region using a HRD detection system developed on polymorphic loci specific to the Chinese population.Methods:A total of 248 ovarian cancer patients admitted to the Yunnan Tumor Hospital between January 2021 and May 2023 were included in this study.The HRD status was evaluated using either the Genomic Scar Score(GSS),which is primarily based on copy number length,type,location,and genomic breakpoints,or the HRD score(a combination of three genomic instability events:allelic loss of heterozygosity(LOH),telomeric allelic imbalance(TAI),and large-scale state transitions(LST)).HRD was defined as positive when the tissue sample had a GSS≥50 or HRD≥42 score,or when harmful BRCA1/2 gene mutation was detected.Results:The study showed that approximately 70.97%of the 248 ovarian cancer patients had a positive HRD status,with a BRCA1/2 gene mutation rate of 30.65%.StageⅢtoⅥstage patients and patients with high-grade serous adenocarcinoma had a higher HRD positivity rate(both P<0.01),and patients with higher HRD scores had a higher frequency of co-occurring other gene mutations(P<0.05).HRD status was associated with pathlogical type,clinical stage and other gene mutations in ovarian cancar(all P<0.01).Conclusion:Ovarian cancer patients in the Yunnan region have a high HRD positivity rate,suggesting that a significant proportion of ovarian cancer patients in this region may benefit from treatment with poly(ADP-ribose)polymerase(PARP)inhibitors.