Germline whole exome sequencing and large-scale replication identifies FANCM as a likely high grade serous ovarian cancer susceptibility gene

E Dicks; H Song; SJ Ramus; E Van Oudenhove; JP Tyrer; MP Intermaggio; S Kar; P Harrington; DD Bowtell; MS Cicek; JM Cunningham; BL Fridley; J Alsop; M Jimenez-Linan; A Piskorz; T Goranova; E Kent; N Siddiqui; J Paul; R Crawford; S Poblete; S Lele; L Sucheston-Campbell; KB Moysich; W Sieh; V McGuire; J Lester; K Odunsi; AS Whittemore; N Bogdanova; M Dürst; P Hillemanns; BY Karlan; A Gentry-Maharaj; U Menon; M Tischkowitz; D Levine; JD Brenton; T Dörk; EL Goode; SA Gayther; PDP Pharoah; E Wozniak; A Ryan; J Ford; N Balogun; C Pye; M Mack; C Luccarini; C Baynes; M Maranian

Journal article

Germline whole exome sequencing and large-scale replication identifies FANCM as a likely high grade serous ovarian cancer susceptibility gene

E Dicks, H Song, SJ Ramus, E Van Oudenhove, JP Tyrer, MP Intermaggio, S Kar, P Harrington, DD Bowtell, MS Cicek, JM Cunningham, BL Fridley, J Alsop, M Jimenez-Linan, A Piskorz, T Goranova, E Kent, N Siddiqui, J Paul, R Crawford Show all

Oncotarget | Published : 2017

DOI: 10.18632/oncotarget.15871

Abstract

We analyzed whole exome sequencing data in germline DNA from 412 high grade serous ovarian cancer (HGSOC) cases from The Cancer Genome Atlas Project and identified 5,517 genes harboring a predicted deleterious germline coding mutation in at least one HGSOC case. Gene-set enrichment analysis showed enrichment for genes involved in DNA repair (p = 1.8×10-3). Twelve DNA repair genes - APEX1, APLF, ATX, EME1, FANCL, FANCM, MAD2L2, PARP2, PARP3, POLN, RAD54L and SMUG1 - were prioritized for targeted sequencing in up to 3,107 HGSOC cases, 1,491 cases of other epithelial ovarian cancer (EOC) subtypes and 3,368 unaffected controls of European origin. We estimated mutation prevalence for each gene an..

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University of Melbourne Researchers

David Bowtell Author

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Grants

Awarded by National Institute for Health Research

Funding Acknowledgements

This work was funded by the American Cancer Society Early Detection Professorship (BYK, SIOP-06-258-01-COUN), the Cancer Councils of New South Wales, Victoria, Queensland, South Australia and Tasmania, the Cancer Foundation of Western Australia, Cancer Research UK (C1005/A7749, C315/A2621, C490/A10119, C490/A10124, C490/A16561, C1005/A12677, C1005/A6383), the Eve Appeal (The Oak Foundation), the Fred C. and Katherine B. Andersen Foundation, the National Institutes for Health (P30 CA016056, P30CA15083, P50CA136393, P50CA159981, R01CA122443, R01CA178535, R01CA61107, R01CA152990 and R01CA086381), the National Center for Advancing Translational Sciences (UL1TR000124), the National Health & Medical Research Council of Australia (NHMRC; ID400413, ID400281), Cancer Australia (509303), the Peter MacCallum Cancer Foundation and Ovarian Cancer Australia (OCA), Roswell Park Cancer Institute Alliance Foundation, Target Ovarian Cancer, the UK Department of Health, the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge and University College London Hospitals Biomedical Research Centre; the U.S. Army Medical Research and Materiel Command (DAMD17-01-1-0729; W81XWH-08-1-0684 and W81XWH-08-1-0685).