多项临床试验已经研究了同源重组缺陷和BRCA1/2基因状态，以选择卵巢癌患者接受聚(ADP核糖)聚合酶酶抑制剂（PARPi）治疗，但对其他DNA损伤响应（DDR）通路关注较少。因此，我们研究了356个DDR基因的外显子和剪接位点区域的体细胞单个/多个核苷酸变异和小插入/缺失，以检查除BRCA1/2以外的基因是否发生改变。对8个高级别浆液性腺癌（HGSC）和4个透明细胞癌（oCCC）患者的全外显子测序数据进行分析。鉴定出28个DDR通路中的42个变异（致病性，可能致病性或变异不确定性）。9个TP53变异中的7个已被介绍于国家癌症基因组图谱卵巢癌中；其他变异发现在28个唯一基因中的23个中，而FAAP24、GTF2H4、POLE4、RPA3和XRCC4中均未报告变异。由于鉴定出的变异不仅限于众所周知的TP53、BRCA1/2和HR相关基因，我们的研究可能有助于更好地了解哪些DDR通路可能影响疾病进展。此外，它们可能作为生物标志物来预测铂类化疗或PARPi治疗反应或疾病进展，因为观察到HGSC和oCCC组中长期存活和短期存活患者之间的DDR通路中断差异。版权所有©2023年国际抗癌研究所（George J. Delinasios博士），保留所有权利。

Several clinical trials have investigated homologous recombination deficiency and BRCA1/2 status to select ovarian cancer patients for treatment with poly(ADP-ribose) polymerase-inhibitors (PARPi), but less attention has been given to other DNA-damage response (DDR) pathways. Therefore, we investigated somatic single/multiple nucleotide variants and small insertions/deletions in exonic and splice-site regions of 356 DDR genes to examine whether genes other than BRCA1/2 are altered.Whole-exome sequencing data from eight high-grade serous adenocarcinoma (HGSC) and four clear cell carcinoma (oCCC) patients were analyzed.Forty-two variants (pathogenic, likely pathogenic or variants of uncertain significance) in 28 genes from DDR pathways were identified. Seven out of nine TP53 variants were previously described in The Cancer Genome Atlas Ovarian Cancer; other variants were found in 23 out of 28 unique genes, whereas no variants were reported in FAAP24, GTF2H4, POLE4, RPA3, and XRCC4.As the identified variants were not only limited to well-known TP53, BRCA1/2, and HR-associated genes, our study might contribute to the better understanding of which DDR pathways potentially influence disease progression. Moreover, they may display a potential role as biomarkers to predict platinum-based chemotherapy or PARPi treatment response or disease progression, as differences in disrupted DDR pathways were observed between patients with long and short overall survival in HGSC and oCCC groups.Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.