| First Author | Krimpenfort P | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 1425 |
| PubMed ID | 30926782 | Mgi Jnum | J:273283 |
| Mgi Id | MGI:6286811 | Doi | 10.1038/s41467-019-09321-8 |
| Citation | Krimpenfort P, et al. (2019) A natural WNT signaling variant potently synergizes with Cdkn2ab loss in skin carcinogenesis. Nat Commun 10(1):1425 |
| abstractText | Cdkn2ab knockout mice, generated from 129P2 ES cells develop skin carcinomas. Here we show that the incidence of these carcinomas drops gradually in the course of backcrossing to the FVB/N background. Microsatellite analyses indicate that this cancer phenotype is linked to a 20 Mb region of 129P2 chromosome 15 harboring the Wnt7b gene, which is preferentially expressed from the 129P2 allele in skin carcinomas and derived cell lines. ChIPseq analysis shows enrichment of H3K27-Ac, a mark for active enhancers, in the 5' region of the Wnt7b 129P2 gene. The Wnt7b 129P2 allele appears sufficient to cause in vitro transformation of Cdkn2ab-deficient cell lines primarily through CDK6 activation. These results point to a critical role of the Cdkn2ab locus in keeping the oncogenic potential of physiological levels of WNT signaling in check and illustrate that GWAS-based searches for cancer predisposing allelic variants can be enhanced by including defined somatically acquired lesions as an additional input. |
