Brief Communication abstract
Nature Genetics 41, 882 - 884 (2009)
Published online: 28 June 2009 | doi:10.1038/ng.403
The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer
Mark M Pomerantz1,11, Nasim Ahmadiyeh1,2,11, Li Jia3, Paula Herman1, Michael P Verzi1, Harshavardhan Doddapaneni4, Christine A Beckwith1, Jennifer A Chan5, Adam Hills1, Matt Davis1, Keluo Yao1, Sarah M Kehoe1, Heinz-Josef Lenz6, Christopher A Haiman6, Chunli Yan3, Brian E Henderson6, Baruch Frenkel7, Jordi Barretina1, Adam Bass1, Josep Tabernero8, José Baselga8, Meredith M Regan9, J Robert Manak4, Ramesh Shivdasani1, Gerhard A Coetzee3 & Matthew L Freedman1,10
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 proto-oncogene. These data provide strong support for a biological mechanism underlying this non-protein-coding risk variant.
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
- Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.
- Department of Urology, Keck School of Medicine of USC, Los Angeles, California, USA.
- Department of Biology and the Roy J. Carver Center for Genomics, University of Iowa, Iowa City, Iowa, USA.
- Department of Pathology and Laboratory Medicine, University of Calgary, Alberta, Canada.
- Department of Preventive Medicine, Keck School of Medicine, Los Angeles, California, USA.
- Institute for Genetic Medicine, Keck School of Medicine, Los Angeles, California, USA.
- Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Catalonia, Spain.
- Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
- The Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
- These authors contributed equally to this work.
Correspondence to: Matthew L Freedman1,10 e-mail: freedman@broad.mit.edu
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