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Mice Lacking a Myc Enhancer Element that Includes Human SNP rs6983267 Are Resistant to Intestinal Tumors

ABSTRACT: 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. Exon-array analysis of mouse colon tissues from Myc-335 null and wild-type mouse (both mice are male and from the same litter). Related ChIP-seq data available in Short Read Archive, Accession ERP001919

ORGANISM(S): Mus musculus

SUBMITTER: Martin Enge

PROVIDER: E-GEOD-41219 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Mice Lacking a Myc Enhancer Element that Includes Human SNP rs6983267 Are Resistant to Intestinal Tumors

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