Loss of imprinting in colorectal cancer linked to hypomethylation of H19 and IGF2
Date
2002Author
Cui, Hengmi
Onyango, Patrick
Brandenburg, Sheri
Wu, Yiqian
Hsieh, Chih-Lin
Feinberg, Andrew P
Type
ArticleLanguage
enMetadata
Show full item recordAbstract
Epigenetic alterations in human cancers include global DNA hypomethylation,gene hypomethylation and promoter hypermethylation, and loss of imprinting (LOI) of the insulin-like growth factor-II gene (IGF2). A mechanism for LOI described previously is hypermethylation of a differentially methylated region (DMR) upstream of the H19 gene, allowing activation of the normally silent maternal allele of IGF2. Here we show that this mechanism does not apply to colorectal cancers, which show hypomethylation of the H19 DMR as well as a DMR upstream of exon 3 of IGF2. This hypomethylation is found in both colorectal cancers and normal mucosa from the same patients, and in cell lines with somatic cell knockout of DNA methyltransferases DNMT1 and DNMT3B. These data suggest that hypomethylation is a mechanism for LOI, that the popular IGF2-H19 enhancer competition model for IGF2 imprinting does not apply to the human colon, and that an alternative model for LOI would involve a transcriptional repressor acting on the normally silent maternal allele of IGF2.
URI
http://cancerres.aacrjournals.org/content/62/22/6442.shorthttp://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/39915
Citation
Cancer Res November 15, 2002 62; 6442Publisher
Univesity of Nairobi Department of Biology