Genetic alterations and their therapeutic implications in epithelial ovarian cancer

BMC Cancer

Yen-Jung Lu¹  Hua-Chien Chen¹  Kien Thiam Tan¹  Hsiao-Yun Lu¹  Chien-Hung Chen¹  Shu-Jen Chen¹  Nina Lapke²  Angel Chao³  Chyong-Huey Lai³  Ting-Chang Chang³ 

[1] ACT Genomics, Co. Ltd., 3F., No.345, Xinhu 2nd Rd., Neihu Dist, 114, Taipei City, Taiwan;ACT Genomics, Co. Ltd., 3F., No.345, Xinhu 2nd Rd., Neihu Dist, 114, Taipei City, Taiwan;ACT Genomics, Co. Ltd., Units 803 – 807, 8F, Building 15W, No.15 Science Park West Avenue, Hong Kong Science Park, Pak Shek Kok. NT, Hong Kong, Hong Kong;Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Linkou Medical Center, 5 Fushin St., Guishan District, 333, Taoyuan, Taiwan;Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, 5 Fushin St., Guishan District, 333, Taoyuan, Taiwan;

关键词: Ovarian cancer;    Histology;    High-grade serous carcinomas;    Endometrioid carcinomas;    Clear cell carcinomas;    Next-generation sequencing;    Genetic alterations;    Signaling pathway;    Targeted therapy;   

DOI  :  10.1186/s12885-021-08233-5

来源: Springer

【 摘 要 】

BackgroundGenetic alterations for epithelial ovarian cancer are insufficiently characterized. Previous studies are limited regarding included histologies, gene numbers, copy number variant (CNV) detection, and interpretation of pathway alteration patterns of individual patients.MethodsWe sequenced 410 genes to analyze mutations and CNV of 82 ovarian carcinomas, including high-grade serous (n = 37), endometrioid (n = 22) and clear cell (n = 23) histologies. Eligibility for targeted therapy was determined for each patient by a pathway-based approach. The analysis covered DNA repair, receptor tyrosine kinase, PI3K/AKT/MTOR, RAS/MAPK, cell cycle, and hedgehog pathways, and included 14 drug targets.ResultsPostulated PARP, MTOR, and CDK4/6 inhibition sensitivity were most common. BRCA1/2 alterations, PTEN loss, and gain of PIK3CA and CCND1 were characteristic for high-grade serous carcinomas. Mutations of ARID1A, PIK3CA, and KRAS, and ERBB2 gain were enriched in the other histologies. PTEN mutations and high tumor mutational burden were characteristic for endometrioid carcinomas. Drug target downstream alterations impaired actionability in all histologies, and many alterations would not have been discovered by key gene mutational analysis. Individual patients often had more than one actionable drug target.ConclusionsGenetic alterations in ovarian carcinomas are complex and differ among histologies. Our results aid the personalization of therapy and biomarker analysis for clinical studies, and indicate a high potential for combinations of targeted therapies.

【 授权许可】

CC BY