학술논문
Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease
Document Type
article
Author
Dhanya Ramachandran; Jonathan P. Tyrer; Stefan Kommoss; Anna DeFazio; Marjorie J. Riggan; AOCS Group; Penelope M. Webb; Peter A. Fasching; Diether Lambrechts; María J. García; Cristina Rodríguez-Antona; Marc T. Goodman; Francesmary Modugno; Kirsten B. Moysich; Beth Y. Karlan; Jenny Lester; Susanne K. Kjaer; Allan Jensen; Estrid Høgdall; Ellen L. Goode; William A. Cliby; Amanika Kumar; Chen Wang; Julie M. Cunningham; Stacey J. Winham; Alvaro N. Monteiro; Joellen M. Schildkraut; Daniel W. Cramer; Kathryn L. Terry; Linda Titus; Line Bjorge; Liv Cecilie Vestrheim Thomsen; OPAL Study Group; Tanja Pejovic; Claus K. Høgdall; Iain A. McNeish; Taymaa May; David G. Huntsman; Jacobus Pfisterer; Ulrich Canzler; Tjoung-Won Park-Simon; Willibald Schröder; Antje Belau; Lars Hanker; Philipp Harter; Jalid Sehouli; Rainer Kimmig; Nikolaus de Gregorio; Barbara Schmalfeldt; Klaus Baumann; Felix Hilpert; Alexander Burges; Boris Winterhoff; Peter Schürmann; Lisa-Marie Speith; Peter Hillemanns; Andrew Berchuck; Sharon E. Johnatty; Susan J. Ramus; Georgia Chenevix-Trench; Paul D. P. Pharoah; Thilo Dörk; Florian Heitz
Source
npj Genomic Medicine, Vol 9, Iss 1, Pp 1-12 (2024)
Subject
Language
English
ISSN
2056-7944
Abstract
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.