美国加利福尼亚大学洛杉矶分校Edward Oconnor研究组研究表明，全基因组生殖系与前列腺癌的表观遗传相关。该研究于2019年10月7日在线发表于《自然—医学》。

他们量化了种系多态性对589个局部前列腺肿瘤的体细胞表观基因组的影响。易感基因位点影响肿瘤的表观基因组，揭示了癌症易感性的机制。他们鉴定并验证了与肿瘤但非恶性组织中甲基化改变有关的1178个基因座。这些肿瘤甲基化的定量性状基因座影响染色质结构以及RNA和蛋白质丰度。一个重要的肿瘤甲基化定量性状基因座与AKT1表达相关，并预测在发现和验证队列中明确的局部治疗后复发。

这些数据揭示了原发肿瘤的生殖系和表观基因组之间的错综复杂的串扰，这可能有助于鉴定侵袭性疾病的生殖系生物标志物，以帮助患者分类，并优化更具侵入性或昂贵的诊断测定方法的使用。

据介绍，肿瘤发生是由种系、环境和随机因素驱动的。尚不清楚它们如何相互作用以产生肿瘤的分子表型。

附：英文原文

Title: Genome-wide germline correlates of the epigenetic landscape of prostate cancer

Author: Kathleen E. Houlahan, Yu-Jia Shiah, Alexander Gusev, Jiapei Yuan, Musaddeque Ahmed, Anamay Shetty, Susmita G. Ramanand, Cindy Q. Yao, Connor Bell, Edward O’Connor, Vincent Huang, Michael Fraser, Lawrence E. Heisler, Julie Livingstone, Takafumi N. Yamaguchi, Alexandre Rouette, Adrien Foucal, Shadrielle Melijah G. Espiritu, Ankit Sinha, Michelle Sam, Lee Timms, Jeremy Johns, Ada Wong, Alex Murison, Michèle Orain, Valérie Picard, Hélène Hovington, Alain Bergeron, Louis Lacombe, Mathieu Lupien, Yves Fradet, Bernard Têtu, John D. McPherson, Bogdan Pasaniuc, Thomas Kislinger, Melvin L. K. Chua, Mark M. Pomerantz, Theodorus van der Kwast, Matthew L. Freedman, Ram S. Mani, Housheng H. He, Robert G. Bristow & Paul C. Boutros 

Issue&Volume: 2019-10-07

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.

DOI: 10.1038/s41591-019-0579-z

Source:https://www.nature.com/articles/s41591-019-0579-z