Although endometrioid carcinoma (EC) and endometrioid ovarian carcinoma (EnOC) display similar pathological features, their molecular characteristics remain to be determined. Somatic mutation data from 2777 EC, 423 EnOC, and 57 endometriosis patients from the Catalogue of Somatic Mutations in Cancer (COSMIC) dataset were analyzed and showed similar profiles with different mutation frequencies among them. By using 275 overlapping mutated genes, EC was clustered into two groups with different disease outcomes and different clinical characteristics. Although BRCA-associated mutation characteristics were identified in both EC and EnOC, the mutation frequencies of BRCA1 (P=0.0146), BRCA2 (P=0.0321), ATR (P=3.25E-11), RAD51 (P=3.95E-08), RAD1 (P=0.0003), TP53 (P=6.11E-33), and BRIP1 (P=2.90E-09) were higher in EnOC. Further analysis showed that EnOC cell lines with BRCA-associated mutation characteristics were more sensitive to poly ADP-ribose polymerase (PARP) inhibitors than EC cell lines, including olaparib, talazoparib, rucaparib, and veliparib. Moreover, based on BRCA-associated mutational and transcriptomic profiles, EC with BRCA-associated mutational burdens shows lower levels of immune cell infiltration, higher expression of immunosuppressive checkpoint molecules and worse prognosis than EC without BRCA mutation. Our study comprehensively analyzed the genome mutation features of EC and EnOC and provide insights into the molecular characteristics of EC and EnOC.
基金:
National Science and Technology Major Sub-Project [2018ZX10301402002]; Technical Innovation Special Project of Hubei Province [2018ACA138]; National Natural Science Foundation of China [81772787, 82072889, 81802601]; Fundamental Research Funds for the Central Universities [2019kfyXMBZ024]
第一作者单位:[1]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Canc Biol Res Ctr,Key Lab,Minist Educ,Wuhan,Hubei,Peoples R China[2]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Dept Gynecol & Obstet,Wuhan,Hubei,Peoples R China
通讯作者:
通讯机构:[1]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Canc Biol Res Ctr,Key Lab,Minist Educ,Wuhan,Hubei,Peoples R China[2]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Dept Gynecol & Obstet,Wuhan,Hubei,Peoples R China
推荐引用方式(GB/T 7714):
Cao Canhui,Yu Ruidi,Gong Wenjian,et al.Genomic mutation features identify distinct BRCA-associated mutation characteristics in endometrioid carcinoma and endometrioid ovarian carcinoma[J].AGING-US.2021,13(22):24686-24709.
APA:
Cao, Canhui,Yu, Ruidi,Gong, Wenjian,Liu, Dan,Zhang, Xiaoxue...&Gao, Qinglei.(2021).Genomic mutation features identify distinct BRCA-associated mutation characteristics in endometrioid carcinoma and endometrioid ovarian carcinoma.AGING-US,13,(22)
MLA:
Cao, Canhui,et al."Genomic mutation features identify distinct BRCA-associated mutation characteristics in endometrioid carcinoma and endometrioid ovarian carcinoma".AGING-US 13..22(2021):24686-24709