Epigenetic lesions at the H19 locus in Wilms' tumour patients

Thomas Moulton, Taria Crenshaw, Yue Hao, Josh Moosikasuwan, Na Lin, Francine Dembitzer, Terrence Hensle, Lawrence Weiss, Lydia McMorrow, Thomas Loew, Wilma Kraus, William Gerald, Benjamin Tycko

Research output: Contribution to journalArticlepeer-review

298 Scopus citations

Abstract

To test the potential role of H19 as a tumour suppressor gene we have examined its expression and DNA methylation in Wilms' tumours (WTs). In most WTs (18/25), H19 RNA was reduced at least 20–fold from fetal kidney levels. Of the expression–negative tumours ten retained 11p15.5 heterozygosity: in nine of these, H19 DNA was biallelically hypermethylated and in two cases hypermethylation locally restricted to H19 sequences was also present in the non–neoplastic kidney parenchyma. IGF2 mRNA was expressed in most but not all WTs and expression patterns were consistent with IGF2/H19 enhancer competition without obligate inverse coupling. These observations implicate genetic and epigenetic inactivation of H19 in Wilms' tumorigenesis.

Original languageEnglish
Pages (from-to)440-447
Number of pages8
JournalNature Genetics
Volume7
Issue number3
DOIs
StatePublished - Jul 1994
Externally publishedYes

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