TY - JOUR
T1 - Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease
AU - OPAL Study Group
AU - AOCS Group
AU - Ramachandran, Dhanya
AU - Tyrer, Jonathan P.
AU - Kommoss, Stefan
AU - DeFazio, Anna
AU - Riggan, Marjorie J.
AU - Webb, Penelope M.
AU - Fasching, Peter A.
AU - Lambrechts, Diether
AU - García, María J.
AU - Rodríguez-Antona, Cristina
AU - Goodman, Marc T.
AU - Modugno, Francesmary
AU - Moysich, Kirsten B.
AU - Karlan, Beth Y.
AU - Lester, Jenny
AU - Kjaer, Susanne K.
AU - Jensen, Allan
AU - Høgdall, Estrid
AU - Goode, Ellen L.
AU - Cliby, William A.
AU - Kumar, Amanika
AU - Wang, Chen
AU - Cunningham, Julie M.
AU - Winham, Stacey J.
AU - Monteiro, Alvaro N.
AU - Schildkraut, Joellen M.
AU - Cramer, Daniel W.
AU - Terry, Kathryn L.
AU - Titus, Linda
AU - Bjorge, Line
AU - Thomsen, Liv Cecilie Vestrheim
AU - Pejovic, Tanja
AU - Høgdall, Claus K.
AU - McNeish, Iain A.
AU - May, Taymaa
AU - Huntsman, David G.
AU - Pfisterer, Jacobus
AU - Canzler, Ulrich
AU - Park-Simon, Tjoung Won
AU - Schröder, Willibald
AU - Belau, Antje
AU - Hanker, Lars
AU - Harter, Philipp
AU - Sehouli, Jalid
AU - Kimmig, Rainer
AU - de Gregorio, Nikolaus
AU - Schmalfeldt, Barbara
AU - Baumann, Klaus
AU - Hilpert, Felix
AU - Winterhoff, Boris
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41525-024-00395-y
DO - 10.1038/s41525-024-00395-y
M3 - Article
C2 - 38443389
AN - SCOPUS:85195145771
SN - 2056-7944
VL - 9
JO - npj Genomic Medicine
JF - npj Genomic Medicine
IS - 1
M1 - 19
ER -