학술논문
Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease
Document Type
article
Author
Ramachandran, Dhanya; Tyrer, Jonathan P; Kommoss, Stefan; DeFazio, Anna; Riggan, Marjorie J; Webb, Penelope M; Fasching, Peter A; Lambrechts, Diether; García, María J; Rodríguez-Antona, Cristina; Goodman, Marc T; Modugno, Francesmary; Moysich, Kirsten B; Karlan, Beth Y; Lester, Jenny; Kjaer, Susanne K; Jensen, Allan; Høgdall, Estrid; Goode, Ellen L; Cliby, William A; Kumar, Amanika; Wang, Chen; Cunningham, Julie M; Winham, Stacey J; Monteiro, Alvaro N; Schildkraut, Joellen M; Cramer, Daniel W; Terry, Kathryn L; Titus, Linda; Bjorge, Line; Thomsen, Liv Cecilie Vestrheim; Pejovic, Tanja; Høgdall, Claus K; McNeish, Iain A; May, Taymaa; Huntsman, David G; Pfisterer, Jacobus; Canzler, Ulrich; Park-Simon, Tjoung-Won; Schröder, Willibald; Belau, Antje; Hanker, Lars; Harter, Philipp; Sehouli, Jalid; Kimmig, Rainer; de Gregorio, Nikolaus; Schmalfeldt, Barbara; Baumann, Klaus; Hilpert, Felix; Burges, Alexander; Winterhoff, Boris; Schürmann, Peter; Speith, Lisa-Marie; Hillemanns, Peter; Berchuck, Andrew; Johnatty, Sharon E; Ramus, Susan J; Chenevix-Trench, Georgia; Pharoah, Paul DP; Dörk, Thilo; Heitz, Florian
Source
npj Genomic Medicine. 9(1)
Subject
Language
Abstract
Survival from ovarian cancer depends on the resection status after primary surgery. We performed genome-wide association analyses for resection status of 7705 ovarian cancer patients, including 4954 with high-grade serous carcinoma (HGSOC), to identify variants associated with residual disease. The most significant association with resection status was observed for rs72845444, upstream of MGMT, in HGSOC (p = 3.9 × 10-8). In gene-based analyses, PPP2R5C was the most strongly associated gene in HGSOC after stage adjustment. In an independent set of 378 ovarian tumours from the AGO-OVAR 11 study, variants near MGMT and PPP2R5C correlated with methylation and transcript levels, and PPP2R5C mRNA levels predicted progression-free survival in patients with residual disease. MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56γ subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.