Epigenomic Enhancer Profiling Defines a Signature of Colon Cancer

被引：264

作者：

Akhtar-Zaidi, Batool ^{[1
,2
]}

Lari, Richard Cowper-Sal ^{[3
]}

Corradin, Olivia ^{[1
]}

Saiakhova, Alina ^{[1
]}

Bartels, Cynthia F. ^{[1
]}

Balasubramanian, Dheepa ^{[1
]}

Myeroff, Lois ^{[4
]}

Lutterbaugh, James ^{[4
]}

Jarrar, Awad ^{[5
]}

Kalady, Matthew F. ^{[4
,5
,6
]}

Willis, Joseph ^{[4
,7
]}

Moore, Jason H. ^{[3
]}

Tesar, Paul J. ^{[1
,4
]}

Laframboise, Thomas ^{[1
,4
]}

Markowitz, Sanford ^{[1
,4
,8
]}

Lupien, Mathieu ^{[3
,9
,10
]}

Scacheri, Peter C. ^{[1
,2
,4
]}

机构：

[1] Case Western Reserve Univ, Dept Genet & Genome Sci, Cleveland, OH 44106 USA

[2] Case Western Reserve Univ, Dept Mol Med, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA

[3] Dartmouth Med Sch, Dept Genet, Norris Cotton Canc Ctr, Inst Quantitat Biomed Sci, Lebanon, NH 03756 USA

[4] Case Western Reserve Univ, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA

[5] Cleveland Clin Fdn, Dept Colorectal Surg, Cleveland, OH 44195 USA

[6] Cleveland Clin Fdn, Lerner Res Inst, Canc Biol Dept, Cleveland, OH 44195 USA

[7] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA

[8] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA

[9] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada

[10] Univ Toronto, Ontario Canc Inst, Univ Hlth Network, Toronto, ON M5G 1L7, Canada

来源：

SCIENCE | 2012年 / 336卷 / 6082期

关键词：

GENOME-WIDE ASSOCIATION; COLORECTAL-CANCER; SUSCEPTIBILITY LOCI; HUMAN BREAST; RISK; 8Q24; METAANALYSIS; CHROMATIN;

D O I：

10.1126/science.1217277

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Cancer is characterized by gene expression aberrations. Studies have largely focused on coding sequences and promoters, even though distal regulatory elements play a central role in controlling transcription patterns. We used the histone mark H3K4me1 to analyze gain and loss of enhancer activity genome-wide in primary colon cancer lines relative to normal colon crypts. We identified thousands of variant enhancer loci (VELs) that comprise a signature that is robustly predictive of the in vivo colon cancer transcriptome. Furthermore, VELs are enriched in haplotype blocks containing colon cancer genetic risk variants, implicating these genomic regions in colon cancer pathogenesis. We propose that reproducible changes in the epigenome at enhancer elements drive a specific transcriptional program to promote colon carcinogenesis.

引用

页码：736 / 739

页数：4

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