| Literature DB >> 31591588 |
Kathleen E Houlahan1,2,3, Yu-Jia Shiah1, Alexander Gusev4,5, Jiapei Yuan6, Musaddeque Ahmed7, Anamay Shetty4,8, Susmita G Ramanand6, Cindy Q Yao1, Connor Bell9, Edward O'Connor9, Vincent Huang1, Michael Fraser1, Lawrence E Heisler1, Julie Livingstone1, Takafumi N Yamaguchi1, Alexandre Rouette1, Adrien Foucal1, Shadrielle Melijah G Espiritu1, Ankit Sinha2,7, Michelle Sam1, Lee Timms1, Jeremy Johns1, Ada Wong1, Alex Murison7, Michèle Orain10, Valérie Picard11, Hélène Hovington11, Alain Bergeron11, Louis Lacombe11, Mathieu Lupien1,2,7, Yves Fradet11, Bernard Têtu10, John D McPherson1, Bogdan Pasaniuc12,13,14, Thomas Kislinger2,7, Melvin L K Chua7,15, Mark M Pomerantz9, Theodorus van der Kwast7,16, Matthew L Freedman9,17,18, Ram S Mani6, Housheng H He2,7, Robert G Bristow19,20,21,22,23,24,25, Paul C Boutros26,27,28,29,30,31,32,33.
Abstract
Oncogenesis is driven by germline, environmental and stochastic factors. It is unknown how these interact to produce the molecular phenotypes of tumors. We therefore quantified the influence of germline polymorphisms on the somatic epigenome of 589 localized prostate tumors. Predisposition risk loci influence a tumor's epigenome, uncovering a mechanism for cancer susceptibility. We identified and validated 1,178 loci associated with altered methylation in tumoral but not nonmalignant tissue. These tumor methylation quantitative trait loci influence chromatin structure, as well as RNA and protein abundance. One prominent tumor methylation quantitative trait locus is associated with AKT1 expression and is predictive of relapse after definitive local therapy in both discovery and validation cohorts. These data reveal intricate crosstalk between the germ line and the epigenome of primary tumors, which may help identify germline biomarkers of aggressive disease to aid patient triage and optimize the use of more invasive or expensive diagnostic assays.Entities:
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Year: 2019 PMID： 31591588 PMCID： PMC7418214 DOI： 10.1038/s41591-019-0579-z
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440