Mice lacking a Myc enhancer that includes human SNP rs6983267 are resistant to intestinal tumors

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

142 Scopus Citations
View graph of relations

Author(s)

  • Inderpreet Kaur Sur
  • Outi Hallikas
  • Anna Vähärautio
  • Mikko Turunen
  • Martin Enge
  • Minna Taipale
  • Auli Karhu
  • Lauri A. Aaltonen
  • Jussi Taipale

Detail(s)

Original languageEnglish
Pages (from-to)1360-1363
Journal / PublicationScience
Volume338
Issue number6112
Publication statusPublished - 7 Dec 2012
Externally publishedYes

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.

Citation Format(s)

Mice lacking a Myc enhancer that includes human SNP rs6983267 are resistant to intestinal tumors. / Sur, Inderpreet Kaur; Hallikas, Outi; Vähärautio, Anna; Yan, Jian; Turunen, Mikko; Enge, Martin; Taipale, Minna; Karhu, Auli; Aaltonen, Lauri A.; Taipale, Jussi.

In: Science, Vol. 338, No. 6112, 07.12.2012, p. 1360-1363.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal