Homologous recombination deficiency status-based classification of high-grade serous ovarian carcinoma
Homologous recombination deficiency status-based classification of high-grade serous ovarian carcinoma
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DOI：
10.1038/s41598-020-59671-3
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发表时间：
2020-02-17
影响因子：
4.6
通讯作者：
Matsumura, Noriomi
中科院分区：
文献类型：
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作者：
Takaya, Hisamitsu;Nakai, Hidekatsu;Matsumura, Noriomi
同源重组修复途径缺陷(HRD)参与了高级别浆液性卵巢癌(HGSOC)的发生、发展以及对铂类化疗药物的敏感性。在这项研究中，我们从癌症基因组图谱(TCGA)获得了关于HGSOC的数据，确定了杂合性丢失、端粒等位基因失衡和大规模状态转换的评分，并计算了HRD评分。然后，我们调查了评分、HRR相关基因的遗传/表观遗传学改变和临床数据之间的关系。我们发现BRCA1/2突变在HRD评分为63分的组中丰富。以63分为HGSOC中HRD病例的最佳分界点。按HRD状态对HGSOC患者进行分类显示，遗传改变(遗传性HRD)引起的HGSOC患者的预后好于表观遗传改变和不明原因引起的HGSOC患者(p=0.0002)。在初次去髓核手术后无肉眼可见残留肿瘤的病例中，12例遗传性HRD中有11例在中位观察期6.6年后存活，存活率非常高(P=0.0059)。综上所述，HGSOC可根据HRD状况分为预后不同的亚型。这种分类对HGSOC的个体化治疗是有用的。
Homologous recombination repair (HRR) pathway deficiency (HRD) is involved in the tumorigenesis and progression of high-grade serous ovarian carcinoma (HGSOC) as well as in the sensitivity to platinum chemotherapy drugs. In this study, we obtained data from The Cancer Genome Atlas (TCGA) on HGSOC and identified scores for the loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions, and calculated the HRD score. We then investigated the relationships among the score, genetic/epigenetic alterations in HRR-related genes, and the clinical data. We found that BRCA1/2 mutations were enriched in the group with HRD scores >= 63. Compared with the groups with scores = 63 to be the best cutoff point for identifying HRD cases in HGSOC. Classification of HGSOC cases by the HRD status revealed a better prognosis for HRD cases caused by genetic alterations (genetic HRD) than those caused by epigenetic changes and those caused by undetermined reasons (p = 0.0002). Among cases without macroscopic residual tumors after primary debulking surgery, 11 of 12 genetic HRD cases survived after the median observation period of 6.6 years, showing remarkably high survival rates (p = 0.0059). In conclusion, HGSOC can be classified into subtypes with different prognoses according to HRD status. This classification could be useful for personalized HGSOC treatment.