文章：

日本癌症基因组与先进疗法中心数据库中子宫内膜癌、卵巢癌及宫颈癌的基因组图谱

Genomic Landscape of Endometrial, Ovarian, and Cervical Cancers in Japan from the Database in the Center for Cancer Genomics and Advanced Therapeutics

原文发布日期：27 December 2023

DOI: 10.3390/cancers16010136

类型: Article

开放获取: 是

英文摘要：

This study aimed to comprehensively clarify the genomic landscape and its association with tumor mutational burden-high (TMB-H, ≥10 mut/Mb) and microsatellite instability-high (MSI-H) in endometrial, cervical, and ovarian cancers. We obtained genomic datasets of a comprehensive genomic profiling test, FoundationOne®CDx, with clinical information using the “Center for Cancer Genomics and Advanced Therapeutics” (C-CAT) database in Japan. Patients can undergo the tests only after standardized treatments under universal health insurance coverage. Endometrial cancers were characterized by a high frequency of TMB-H and MSI-H, especially in endometrioid carcinomas. The lower ratio ofPOLEexonuclease mutations and the higher ratio ofTP53mutations compared to previous reports suggested the prognostic effects of the molecular subtypes. Among the 839 cervical cancer samples, frequent mutations ofKRAS,TP53,PIK3CA,STK11,CDKN2A, andERBB2were observed in adenocarcinomas, whereas the ratio of TMB-H was significantly higher in squamous cell carcinomas. Among the 1606 ovarian cancer samples, genomic profiling of serous, clear cell, endometrioid, and mucinous carcinomas was characterized. Pathogenic mutations in thePOLEexonuclease domain were associated with high TMB, and the mutation ratio was low in both cervical and ovarian cancers. The C-CAT database is useful for determining the mutational landscape of each cancer type and histological subtype. As the dataset is exclusively collected from patients after the standardized treatments, the information on “druggable” alterations highlights the unmet needs for drug development in major gynecological cancers.

摘要翻译： 

本研究旨在全面阐明子宫内膜癌、宫颈癌和卵巢癌的基因组特征及其与高肿瘤突变负荷（TMB-H，≥10个突变/Mb）和高微卫星不稳定性（MSI-H）的关联。我们通过日本“癌症基因组学与先进治疗中心”（C-CAT）数据库，获取了包含临床信息的综合性基因组分析检测FoundationOne®CDx的基因组数据集。患者需在全民健康保险覆盖下完成标准化治疗后，方可接受此项检测。子宫内膜癌表现出较高的TMB-H和MSI-H频率，尤其在子宫内膜样癌中更为显著。与既往研究相比，POLE核酸外切酶结构域突变比例较低而TP53突变比例较高，提示分子亚型对预后的影响。在839例宫颈癌样本中，腺癌中常见KRAS、TP53、PIK3CA、STK11、CDKN2A和ERBB2突变，而鳞状细胞癌的TMB-H比例显著更高。通过对1606例卵巢癌样本的分析，明确了浆液性癌、透明细胞癌、子宫内膜样癌和黏液性癌的基因组特征。POLE核酸外切酶结构域的致病性突变与高TMB相关，而该突变在宫颈癌和卵巢癌中的发生率均较低。C-CAT数据库有助于确定各类癌症及其组织学亚型的突变特征。由于该数据集专门收集自标准化治疗后的患者，其中“可靶向”变异信息凸显了主要妇科恶性肿瘤在药物开发领域尚未满足的临床需求。

原文链接：

Genomic Landscape of Endometrial, Ovarian, and Cervical Cancers in Japan from the Database in the Center for Cancer Genomics and Advanced Therapeutics