The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer.
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.
Pomerantz
Mark M
MM
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Ahmadiyeh
Nasim
N
Jia
Li
L
Herman
Paula
P
Verzi
Michael P
MP
Doddapaneni
Harshavardhan
H
Beckwith
Christine A
CA
Chan
Jennifer A
JA
Hills
Adam
A
Davis
Matt
M
Yao
Keluo
K
Kehoe
Sarah M
SM
Lenz
Heinz-Josef
HJ
Haiman
Christopher A
CA
Yan
Chunli
C
Henderson
Brian E
BE
Frenkel
Baruch
B
Barretina
Jordi
J
Bass
Adam
A
Tabernero
Josep
J
Baselga
José
J
Regan
Meredith M
MM
Manak
J Robert
JR
Shivdasani
Ramesh
R
Coetzee
Gerhard A
GA
Freedman
Matthew L
ML
D000483:Alleles; D045744:Cell Line, Tumor; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011485:Protein Binding; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D051820:TCF Transcription Factors / Q000378:metabolism; D058118:Transcription Factor 7-Like 2 Protein
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein