Cistrome Partitioning Reveals Convergence of Somatic Mutations and Risk Variants on Master Transcription Regulators in Primary Prostate Tumors.,Cancer Cell

当前位置： X-MOL 学术 › Cancer Cell › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Cistrome Partitioning Reveals Convergence of Somatic Mutations and Risk Variants on Master Transcription Regulators in Primary Prostate Tumors.
Cancer Cell ( IF 50.3 ) Pub Date : 2019-11-14 , DOI: 10.1016/j.ccell.2019.10.005
Parisa Mazrooei ₁ , Ken J Kron ₂ , Yanyun Zhu ₃ , Stanley Zhou ₁ , Giacomo Grillo ₂ , Tahmid Mehdi ₂ , Musaddeque Ahmed ₂ , Tesa M Severson ₃ , Paul Guilhamon ₂ , Nicholas Sinnott Armstrong ₄ , Vincent Huang ₅ , Takafumi N Yamaguchi ₅ , Michael Fraser ₆ , Theodorus van der Kwast ₇ , Paul C Boutros ₈ , Housheng Hansen He ₁ , Andries M Bergman ₃ , Robert G Bristow ₉ , Wilbert Zwart ₁₀ , Mathieu Lupien ₁₁

Affiliation

Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Division of Oncogenomics, Oncode Institute, the Netherlands Cancer Institute, Amsterdam, The Netherlands.
Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
Department of Pathology and Laboratory Medicine, Toronto General Hospital, University Health Network, Toronto, ON M5G 2C4, Canada.
Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada.
CRUK Manchester Institute and Manchester Cancer Research Centre, University of Manchester, Manchester M20 4GJ, UK.
Division of Oncogenomics, Oncode Institute, the Netherlands Cancer Institute, Amsterdam, The Netherlands; Laboratory of Chemical Biology and Institute for Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.

Thousands of noncoding somatic single-nucleotide variants (SNVs) of unknown function are reported in tumors. Partitioning the genome according to cistromes reveals the enrichment of somatic SNVs in prostate tumors as opposed to adjacent normal tissue cistromes of master transcription regulators, including AR, FOXA1, and HOXB13. This parallels enrichment of prostate cancer genetic predispositions over these transcription regulators' tumor cistromes, exemplified at the 8q24 locus harboring both risk variants and somatic SNVs in cis-regulatory elements upregulating MYC expression. However, Massively Parallel Reporter Assays reveal that few SNVs can alter the transactivation potential of individual cis-regulatory elements. Instead, similar to inherited risk variants, SNVs accumulate in cistromes of master transcription regulators required for prostate cancer development.

中文翻译：

Cistrome分区揭示了原发性前列腺癌中主要转录调节子的体细胞突变和风险变异的融合。

肿瘤中报道了成千上万个功能未知的非编码体单核苷酸变体（SNV）。根据cistromes划分基因组揭示了前列腺肿瘤中体细胞SNV的富集，这与主转录调节剂（包括AR，FOXA1和HOXB13）的相邻正常组织cistroms相反。这与这些转录调节因子的肿瘤富集的前列腺癌遗传易感性相似，例如在8q24位点，其在上调MYC表达的顺式调控元件中既包含风险变体，又包含体细胞SNV。但是，大规模平行报道者试验表明，很少有SNV可以改变单个顺式调节元件的反式激活潜能。相反，类似于继承的风险变体，

更新日期：2019-11-14

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南

全部期刊列表>>