PO.CL07.01 · 临床研究
印度卵巢癌的基因组图谱及同源重组缺陷模式：对精准治疗的临床意义
Genomic landscape and patterns of homologous recombination deficiency in Indian ovarian cancer: Clinical implications for precision therapy
该海报暂无可下载的资料
AACR 官方页面
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
引言：卵巢癌仍是全球女性癌症相关死亡的主要原因之一。然而，印度人群卵巢癌的基因组特征尚未得到充分界定，这限制了对特定血统肿瘤生物学特征和潜在治疗靶点的认识。
方法：分析了来自印度患者的619份卵巢肿瘤样本的全外显子组测序数据。经过严格的质量控制和过滤后，整理出5,244个优先级体细胞变异，并根据AMP指南进行分类。将同源重组缺陷（HRD）评分与临床元数据整合，以考察同源重组修复（HRR）基因改变、HRD状态与临床病理特征之间的关联。
结果：该队列的中位HRD评分为47，47%的肿瘤被归类为HRD阳性。在临床报告的变异中，28.2%被归类为致病性或可能致病性（P/LP），49.5%为意义未明变异（VUS），22.1%仍未分类。反复发生改变的驱动基因包括TP53（64.9%）、BRCA1（38.6%）、RAD50（37.5%）、CHEK1（21.2%）和POLE（17.9%），表明DNA损伤反应（DDR）和HRR通路广泛受损。约40.7%的肿瘤中检测到BRCA1/2 P/LP变异。HRD阳性在BRCA突变（48.0%）和非BRCA突变肿瘤（46.3%）中均被发现，提示HRR缺陷不仅限于BRCA1/2改变，还涉及RAD50、MRE11、CHEK1、CHEK2、FANCA和FANCD2等基因。按年龄分层分析显示，各年龄组中BRCA1/2改变和HRD阳性的频率一致（每层40-50%），表明HRR通路损伤在各临床亚组中普遍存在。
结论：本研究是印度人群卵巢癌规模最大的基于外显子组的分析之一。近一半的肿瘤表现出HRD，即使在没有BRCA1/2突变的情况下，HRR通路损伤也很常见。这些发现凸显了全面的HRR基因检测和HRD评估对于为印度卵巢癌患者提供精准肿瘤学策略（包括使用PARP抑制剂和铂类治疗）的重要性。
关键词：卵巢癌，印度人群，外显子组测序，同源重组缺陷，BRCA1，TP53，DNA修复，PARP抑制剂，精准肿瘤学。
查看英文原文 English abstract
Introduction: Ovarian carcinoma remains a leading cause of cancer-related mortality among women globally. However, the genomic characteristics of ovarian cancer in the Indian population are not well defined, limiting insights into ancestry-specific tumor biology and potential therapeutic targets.
Methodology: Whole-exome sequencing data from 619 ovarian tumor samples from Indian patients were analyzed. After stringent quality control and filtering, 5,244 prioritized somatic variants were curated and classified according to AMP guidelines. Homologous recombination deficiency (HRD) scores were integrated with clinical metadata to examine associations between homologous recombination repair (HRR) gene alterations, HRD status, and clinicopathological features.
Results: The median HRD score across the cohort was 47, with 47% of tumors classified as HRD-positive. Among clinically reported variants, 28.2% were classified as pathogenic or likely pathogenic (P/LP), 49.5% as variants of uncertain significance (VUS), and 22.1% remained unclassified. Recurrently altered driver genes included TP53 (64.9%), BRCA1 (38.6%), RAD50 (37.5%), CHEK1 (21.2%), and POLE (17.9%), indicating extensive disruption of DNA damage response (DDR) and HRR pathways. BRCA1/2 P/LP variants were detected in approximately 40.7% of tumors. HRD positivity was identified in both BRCA -mutated (48.0%) and non- BRCA -mutated tumors (46.3%), suggesting that HRR deficiency extends beyond BRCA1/2 alterations to include genes such as RAD50 , MRE11 , CHEK1 , CHEK2 , FANCA,andFANCD2 .Age-stratified analysis showed consistent frequencies of BRCA1/2 alterations and HRD positivity across all age groups (40-50% per stratum), indicating that HRR pathway disruption is widespread across clinical subgroups.
Conclusions: This study represents one of the largest exome-based analyses of ovarian cancer in the Indian population. Nearly half of the tumors demonstrated HRD, and HRR pathway disruption was frequent even in the absence of BRCA1/2 mutations. These findings highlight the importance of comprehensive HRR gene testing and HRD evaluation to inform precision oncology approaches, including the use of PARP inhibitors and platinum-based therapies, for Indian ovarian cancer patients.
Keywords: Ovarian carcinoma, Indian population, exome sequencing, homologous recombination deficiency, BRCA1 , TP53 , DNA repair, PARP inhibitors, precision oncology.
利益披露 Disclosure
R. Katara, None..
S. Kumar, None..
A. Agarwal, None..
K. Kumar, None..
D. K. Sharma, None..
Y. M, None..
H. Singh, None..
V. Kumar, None..
S. Sharma, None.