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Mice Lacking a Myc Enhancer That Includes Human SNP rs6983267 Are Resistant to Intestinal Tumors
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Mice Lacking a Myc Enhancer That Includes Human SNP rs6983267 Are Resistant to Intestinal Tumors
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Journal Article
Mice Lacking a Myc Enhancer That Includes Human SNP rs6983267 Are Resistant to Intestinal Tumors
2012
Overview
Multiple cancer-associated single-nucleotide polymorphisms (SNPs) have been mapped to conserved sequences within a 500-kilobase region upstream of the MYC oncogene on human chromosome 8q24. These SNPs may affect cancer development through altered regulation of MYC expression, but this hypothesis has been difficult to confirm. We generated mice deficient in Myc-335, a putative MYC regulatory element that contains rs6983267, a SNP accounting for more human cancer-related morbidity than any other genetic variant or mutation. In Myc-335 null mice, Myc transcripts were expressed in the intestinal crypts in a pattern similar to that in wild-type mice but at modestly reduced levels. The mutant mice displayed no overt phenotype but were markedly resistant to intestinal tumorigenesis induced by the APCmin mutation. These results establish that a cancer-associated SNP identified in human genome-wide association studies has a functional effect in vivo.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
Adenomatous Polyposis Coli - genetics
/ Adenomatous Polyposis Coli - pathology
/ Alleles
/ Animal tumors. Experimental tumors
/ Animals
/ Biological and medical sciences
/ Cancer
/ Cell Transformation, Neoplastic - genetics
/ Colon
/ Control
/ Crypts
/ Enhancer Elements, Genetic - genetics
/ Exons
/ Experimental digestive system and abdominal tumors
/ genome-wide association study
/ Human
/ Humans
/ Intestinal Neoplasms - genetics
/ Intestinal Neoplasms - pathology
/ Mice
/ Mutation
/ Polymorphism, Single Nucleotide
/ Proto-Oncogene Proteins c-myc - genetics
/ Risk
/ Rodents
/ Single nucleotide polymorphism
/ Tumors
/ Upstream
