Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease

Ramachandran D, Tyrer JP, Kommoss S, DeFazio A, Riggan MJ, Webb PM, Fasching P, Lambrechts D, García MJ, Rodríguez-Antona C, Goodman MT, Modugno F, Moysich KB, Karlan BY, Lester J, Kjaer SK, Jensen A, Høgdall E, Goode EL, Cliby WA, Kumar A, Wang C, Cunningham JM, Winham SJ, Monteiro AN, Schildkraut JM, Cramer DW, Terry KL, Titus L, Bjorge L, Thomsen LCV, Pejovic T, Høgdall CK, McNeish IA, May T, Huntsman DG, Pfisterer J, Canzler U, Park-Simon TW, Schröder W, Belau A, Hanker L, Harter P, Sehouli J, Kimmig R, de Gregorio N, Schmalfeldt B, Baumann K, Hilpert F, Burges A, Winterhoff B, Schürmann P, Speith LM, Hillemanns P, Berchuck A, Johnatty SE, Ramus SJ, Chenevix-Trench G, Pharoah PD, Dörk T, Heitz F, Bowtell D, Fereday S, Traficante N, Hung J, Friedlander M, Obermair A, Grant P, Beesley V, Blomfield P, Brand A, Davis A, Leung Y, Nicklin J, Quinn M, Livingstone K, O’Neill H, Williams M (2024)


Publication Type: Journal article

Publication year: 2024

Journal

Book Volume: 9

Article Number: 19

Journal Issue: 1

DOI: 10.1038/s41525-024-00395-y

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.

Authors with CRIS profile

Involved external institutions

Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) University of Cambridge GB United Kingdom (GB) Universitätsklinikum Tübingen DE Germany (DE) University of Sydney (USYD) AU Australia (AU) Duke University Medical Center US United States (USA) (US) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) AU Australia (AU) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven BE Belgium (BE) Universidad Rey Juan Carlos ES Spain (ES) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) ES Spain (ES) Cedars-Sinai Medical Center US United States (USA) (US) University of Pittsburgh US United States (USA) (US) University of California Los Angeles (UCLA) US United States (USA) (US) Haukeland University Hospital / Haukeland universitetssykehus NO Norway (NO) Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Klinikum der Universität München DE Germany (DE) University of New South Wales (UNSW) AU Australia (AU) Roswell Park Cancer Institute US United States (USA) (US) Danish Cancer Society Research Center DK Denmark (DK) Gentofte Hospital DK Denmark (DK) Mayo Clinic US United States (USA) (US) H. Lee Moffitt Cancer Center & Research Institute US United States (USA) (US) Emory University US United States (USA) (US) Dartmouth Cancer Center US United States (USA) (US) Medford Women’s Clinic US United States (USA) (US) Rigshospitalet DK Denmark (DK) Imperial College London / The Imperial College of Science, Technology and Medicine GB United Kingdom (GB) University Health Network (UHN) CA Canada (CA) University of British Columbia CA Canada (CA) Brigham and Women's Hospital (BWH) US United States (USA) (US) Universitätsklinikum Carl Gustav Carus Dresden DE Germany (DE) Klinikverbund Bremen (Gesundheit Nord) DE Germany (DE) Universitätsmedizin Greifswald / Universitätsklinikum Greifswald DE Germany (DE) Universitätsklinikum Frankfurt am Main (KGU) DE Germany (DE) Kliniken Essen-Mitte DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Universitätsklinikum Essen DE Germany (DE) Universitätsklinikum Ulm DE Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Universitätsklinikum Gießen und Marburg (UKGM) DE Germany (DE) University of Minnesota (UMN) US United States (USA) (US) Peter MacCallum Cancer Centre AU Australia (AU) Westmead Hospital AU Australia (AU)

How to cite

APA:

Ramachandran, D., Tyrer, J.P., Kommoss, S., DeFazio, A., Riggan, M.J., Webb, P.M.,... Williams, M. (2024). Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease. npj Genomic Medicine, 9(1). https://doi.org/10.1038/s41525-024-00395-y

MLA:

Ramachandran, Dhanya, et al. "Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease." npj Genomic Medicine 9.1 (2024).

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