Journal article

PPM1D Mosaic Truncating Variants in Ovarian Cancer Cases May Be Treatment-Related Somatic Mutations

Paul DP Pharoah, Honglin Song, Ed Dicks, Maria P Intermaggio, Patricia Harrington, Caroline Baynes, Kathryn Alsop, Natalia Bogdanova, Mine S Cicek, Julie M Cunningham, Brooke L Fridley, Aleksandra Gentry-Maharaj, Peter Hillemanns, Shashi Lele, Jenny Lester, Valerie McGuire, Kirsten B Moysich, Samantha Poblete, Weiva Sieh, Lara Sucheston-Campbell Show all



Mosaic truncating mutations in the protein phosphatase, Mg(2+)/Mn(2+)-dependent, 1D (PPM1D) gene have recently been reported with a statistically significantly greater frequency in lymphocyte DNA from ovarian cancer case patients compared with unaffected control patients. Using massively parallel sequencing (MPS) we identified truncating PPM1D mutations in 12 of 3236 epithelial ovarian cancer (EOC) case patients (0.37%) but in only one of 3431 unaffected control patients (0.03%) (P = .001). All statistical tests were two-sided. A combination of Sanger sequencing, pyrosequencing, and MPS data suggested that 12 of the 13 mutations were mosaic. All mutations were identified in post-chemotherapy..

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Awarded by Cancer Research UK

Awarded by National Institutes for Health

Awarded by National Health & Medical Research Council of Australia (NHMRC)

Awarded by US Army Medical Research and Materiel Command

Awarded by Cancer Research UK; The Francis Crick Institute

Funding Acknowledgements

This work was funded by the Cancer Councils of New South Wales, Victoria, Queensland, South Australia and Tasmania, the Cancer Foundation of Western Australia, Cancer Research UK (C315/A2621, C490/A10119, C490/A10124, C490/A16561, C490/A6187, C1005/A12677, C1005/A6383, C1005/A7749), the Eve Appeal (The Oak Foundation), the National Institutes for Health (P30CA014089, P30CA016056, P30CA15083, P50CA136393, P50CA159981, R01CA122443, R01CA178535, R01CA61107, R01CA152990, and R01CA086381), the National Health & Medical Research Council of Australia (NHMRC; ID400413, ID400281), the Pomeranian Medical University, Queensland Cancer Fund, Roswell Park Cancer Institute Alliance Foundation, the Rudolf Bartling Foundation, the UK Department of Health, the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge and at the University College London Hospitals, and the US Army Medical Research and Materiel Command (DAMD17-01-1-0729).