E-GEOD-45341 - Fundamental differences in promoter CpG island DNA hypermethylation between human cancer and genetically engineered mouse models of cancer [RRBS]
Released on 10 October 2013, last updated on 25 November 2013
Homo sapiens, Mus musculus
Genetic and epigenetic alterations are essential for the initiation and progression of human cancer. We previously reported that primary human medulloblastomas showed extensive cancer-specific CpG island DNA hypermethylation in critical developmental pathways. To determine whether genetically engineered mouse models (GEMMs) of medulloblastoma have comparable epigenetic changes, we assessed genome-wide DNA methylation in three mouse models of medulloblastoma. In contrast to human samples, very few loci with cancer-specific DNA hypermethylation were detected, and in almost all cases the degree of methylation was relatively modest compared to the dense hypermethylation in the human cancers. To determine if this finding was common to other GEMMs, we examined a Burkitt lymphoma and breast cancer model and did not detect promoter CpG island DNA hypermethylation, suggesting that human cancers and at least some GEMMs are fundamentally different with respect to this epigenetic modification. These findings provide an opportunity to both better understand the mechanism of aberrant DNA methylation in human cancer and construct better GEMMs to serve as preclinical platforms for therapy development. Examination of DNA methylation in one representative human medulloblastoma patient sample and three different mouse models of medulloblastoma using RRBS
methylation profiling by high throughput sequencing
Scott J. Diede <email@example.com>, Ashlee E Tyler, C C Keyes, Christopher J Kemp, Christopher S Hackett, James M Olson, Joyoti Dey, Katrina Elsaesser, Paul E Neiman, Scott J Diede, Stephen J Tapscott, William A Weiss, Zizhen Yao
Fundamental differences in promoter CpG island DNA hypermethylation between human cancer and genetically engineered mouse models of cancer. Diede SJ, Yao Z, Keyes CC, Tyler AE, Dey J, Hackett CS, Elsaesser K, Kemp CJ, Neiman PE, Weiss WA, Olson JM, Tapscott SJ.