TY - JOUR
T1 - PPM1D Mosaic Truncating Variants in Ovarian Cancer Cases May Be Treatment-Related Somatic Mutations
AU - Ovarian Cancer Association Consortium
AU - Australian Ovarian Cancer Study Group
AU - Pharoah, Paul D.P.
AU - Song, Honglin
AU - Dicks, Ed
AU - Intermaggio, Maria P.
AU - Harrington, Patricia
AU - Baynes, Caroline
AU - Alsop, Kathryn
AU - Bogdanova, Natalia
AU - Cicek, Mine S.
AU - Cunningham, Julie M.
AU - Fridley, Brooke L.
AU - Gentry-Maharaj, Aleksandra
AU - Hillemanns, Peter
AU - Lele, Shashi
AU - Lester, Jenny
AU - McGuire, Valerie
AU - Moysich, Kirsten B.
AU - Poblete, Samantha
AU - Sieh, Weiva
AU - Sucheston-Campbell, Lara
AU - Widschwendter, Martin
AU - Whittemore, Alice S.
AU - Dörk, Thilo
AU - Menon, Usha
AU - Odunsi, Kunle
AU - Goode, Ellen L.
AU - Karlan, Beth Y.
AU - Bowtell, David D.
AU - Gayther, Simon A.
AU - Ramus, Susan J.
AU - Wozniak, E.
AU - Ryan, A.
AU - Ford, J.
AU - Balogun, N.
AU - Mack, Marie
AU - Luccarini, Craig
N1 - Publisher Copyright:
© 2016 The Author 2016. Published by Oxford University Press. All rights reserved.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - Mosaic truncating mutations in the protein phosphatase, Mg2+/Mn2+-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.
AB - Mosaic truncating mutations in the protein phosphatase, Mg2+/Mn2+-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.
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U2 - 10.1093/jnci/djv347
DO - 10.1093/jnci/djv347
M3 - Article
C2 - 26823519
AN - SCOPUS:84962612922
SN - 0027-8874
VL - 108
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 3
ER -