机构:[1]Department of Obstetrics and Gynecology, National Clinical Research Centre for Obstetric and Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.[2]Geneplus institute, Beijing, China.[3]Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.[4]Department of Gynecology Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.[5]Geneplus-Shenzhen, Shenzhen, China.[6]Department of Obstetrics and Gynecolgoy, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.[7]Department of Gynecological Oncology, First Hospital of Jilin University, Changchun, China.[8]Department of Obstetrics and Gynecology, West China Second Hospital of Sichuan University, Chengdu, China.[9]Department of Obstetrics and Gynecology, Peking University International Hospital, Beijing, China.[10]Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi’an Jiaotong University, Shaanxi, China.[11]Department of Gynecology Oncology, Harbin Medical University Cancer Hospital, Harbin, China.[12]Department of Gynecology, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China.[13]Department of Gynecologic Oncology, Sichuan Cancer Hospital, Chengdu, China.四川省肿瘤医院
Epithelial ovarian cancer (EOC) is classified into five major histotypes: high-grade serous (HGSOC), low-grade serous (LGSOC), clear cell (CCOC), endometrioid (ENOC), and mucinous (MOC). However, the landscape of molecular and immunological alterations in these histotypes, especially LGSOC, CCOC, ENOC, and MOC, is largely uncharacterized. We collected 101 treatment-naive EOC patients. The resected tumor tissues and paired preoperative peripheral blood samples were collected and subjected to target sequencing of 1021 cancer-associated genes and T cell repertoire sequencing. Distinct characteristics of mutations were identified among the five histotypes. Furthermore, tumor mutation burden (TMB) was found to be higher in CCOC and ENOC, but lower in LGSOC and HGSOC. Alterations associated with DNA damage repair (DDR) pathways and homologous recombination deficiencies (HRD) were prevalent in five histotypes. CCOC demonstrated increased level of T cell clonality compared with HSGOC. Interestingly, the proportion of the 100 most common T cell clones was associated with TMB and tumor neoantigen burden in CCOC, highlighting more sensitive anti-tumor responses in this histotype, which was also evidenced by the enhanced convergent recombination of T cell clones. These findings shed light on the molecular traits of genomic alteration and T cell repertoire in the five major EOC histotypes and may help optimize clinical management of EOC with different histotypes.
基金:
National Natural Science Foundation of China [81772783, 81971475]; Chinese Academy of Medical Sciences Initiative for Innovative Medicine [CAMS-2017-I2M-1-002]
第一作者机构:[1]Department of Obstetrics and Gynecology, National Clinical Research Centre for Obstetric and Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
共同第一作者:
通讯作者:
推荐引用方式(GB/T 7714):
Zhu Shan,Zhang Chunliu,Cao Dongyan,et al.Genomic and TCR profiling data reveal the distinct molecular traits in epithelial ovarian cancer histotypes[J].ONCOGENE.2022,41(22):3093-3103.doi:10.1038/s41388-022-02277-y.
APA:
Zhu, Shan,Zhang, Chunliu,Cao, Dongyan,Bai, Jing,Yu, Shuangni...&Xiang, Yang.(2022).Genomic and TCR profiling data reveal the distinct molecular traits in epithelial ovarian cancer histotypes.ONCOGENE,41,(22)
MLA:
Zhu, Shan,et al."Genomic and TCR profiling data reveal the distinct molecular traits in epithelial ovarian cancer histotypes".ONCOGENE 41..22(2022):3093-3103