| Literature DB >> 26823519 |
Paul D P Pharoah1, Honglin Song1, Ed Dicks1, Maria P Intermaggio1, Patricia Harrington1, Caroline Baynes1, Kathryn Alsop1, Natalia Bogdanova1, Mine S Cicek1, Julie M Cunningham1, Brooke L Fridley1, Aleksandra Gentry-Maharaj1, Peter Hillemanns1, Shashi Lele1, Jenny Lester1, Valerie McGuire1, Kirsten B Moysich1, Samantha Poblete1, Weiva Sieh1, Lara Sucheston-Campbell1, Martin Widschwendter1, Alice S Whittemore1, Thilo Dörk1, Usha Menon1, Kunle Odunsi1, Ellen L Goode1, Beth Y Karlan1, David D Bowtell1, Simon A Gayther1, Susan J Ramus1.
Abstract
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 treatment blood samples from case patients (n = 1827) (average 1234 days post-treatment in carriers) rather than from cases collected pretreatment (less than 14 days after diagnosis, n = 1384) (P = .002). These data suggest that PPM1D variants in EOC cases are primarily somatic mosaic mutations caused by treatment and are not associated with germline predisposition to EOC.Entities:
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Year: 2016 PMID： 26823519 PMCID： PMC5072371 DOI： 10.1093/jnci/djv347
Source DB: PubMed Journal: J Natl Cancer Inst ISSN： 0027-8874 Impact factor: 13.506