The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer

被引:517
作者
Pomerantz, Mark M. [1 ]
Ahmadiyeh, Nasim [1 ,2 ]
Jia, Li [3 ]
Herman, Paula [1 ]
Verzi, Michael P. [1 ]
Doddapaneni, Harshavardhan [4 ]
Beckwith, Christine A. [1 ]
Chan, Jennifer A. [5 ]
Hills, Adam [1 ]
Davis, Matt [1 ]
Yao, Keluo [1 ]
Kehoe, Sarah M. [1 ]
Lenz, Heinz-Josef [6 ]
Haiman, Christopher A. [6 ]
Yan, Chunli [3 ]
Henderson, Brian E. [6 ]
Frenkel, Baruch [7 ]
Barretina, Jordi [1 ]
Bass, Adam [1 ]
Tabernero, Josep [8 ]
Baselga, Jose [8 ]
Regan, Meredith M. [9 ]
Manak, J. Robert [4 ]
Shivdasani, Ramesh [1 ]
Coetzee, Gerhard A. [3 ]
Freedman, Matthew L. [1 ,10 ,11 ]
机构
[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA
[3] USC, Keck Sch Med, Dept Urol, Los Angeles, CA USA
[4] Univ Iowa, Dept Biol, Iowa City, IA 52242 USA
[5] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB T2N 1N4, Canada
[6] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA
[7] Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA
[8] Vall Hebron Univ Hosp, Vall Hebron Inst Oncol, Catalonia, Spain
[9] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA
[10] Broad Inst Harvard, Cambridge, MA USA
[11] MIT, Cambridge, MA 02139 USA
基金
美国国家卫生研究院;
关键词
WIDE ASSOCIATION SCAN; CHROMOSOME; 8Q24; BETA-CATENIN; GENOME; ACTIVATION; ENHANCERS; PROSTATE; APC;
D O I
10.1038/ng.403
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
An inherited variant on chromosome 8q24, rs6983267, is significantly associated with cancer pathogenesis. We present evidence that the region harboring this variant is a transcriptional enhancer, that the alleles of rs6983267 differentially bind transcription factor 7-like 2 (TCF7L2) and that the risk region physically interacts with the MYC protooncogene. These data provide strong support for a biological mechanism underlying this non-protein-coding risk variant.
引用
收藏
页码:882 / 884
页数:3
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