Hypomethylation and aberrant expression of the glioma pathogenesis-related 1 gene in Wilms tumors

Laxmi Chilukamarri, Anne L. Hancock, Sally Malik, Joanna Zabkiewicz, Jenny A. Baker, Alexander Greenhough, Anthony R. Dallosso, Tim Hui Ming Huang, Brigitte Royer-Pokora, Keith W. Brown, Karim Malik

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Wilms tumors (WTs) have a complex etiology, displaying genetic and epigenetic changes, including loss of imprinting (LOI) and tumor suppressor gene silencing. To identify new regions of epigenetic perturbation in WTs, we screened kidney and tumor DNA using CpG island (CGI) tags associated with cancer-specific DNA methylation changes. One such tag corresponded to a paralog of the glioma pathogenesis-related 1/related to testis-specific, vespid, and pathogenesis proteins 1 (GLIPR1/RTVP-1) gene, previously reported to be a tumor-suppressor gene silenced by hypermethylation in prostate cancer. Here we report methylation analysis of the GLIPR1/RTVP-1 gene in WTs and normal fetal and pediatric kidneys. Hypomethylation of the GLIPR1/RTVP-1 5′-region in WTs relative to normal tissue is observed in 21/24 (87.5%) of WTs analyzed. Quantitative analysis of GLIPR1/RTVP-1 expression in 24 WTs showed elevated transcript levels in 16/24 WTs (67%), with 12 WTs displaying in excess of 20-fold overexpression relative to fetal kidney (FK) control samples. Immunohistochemical analysis of FK and WT corroborates the RNA expression data and reveals high GLIPR1/RTVP-1 in WT blastemal cells together with variable levels in stromal and epithelial components. Hypomethylation is also evident in the WT precursor lesions and nephrogenic rests (NRs), supporting a role for GLIPR1/RTVP-1 deregulation early in Wilms tumorigenesis. Our data show that, in addition to gene dosage changes arising from LOI and hypermethylation-induced gene silencing, gene activation resulting from hypomethylation is also prevalent in WTs.

Original languageEnglish (US)
Pages (from-to)970-978
Number of pages9
JournalNeoplasia
Volume9
Issue number11
DOIs
StatePublished - Nov 2007
Externally publishedYes

Keywords

  • Epigenetics
  • GLIPR1/RTVP-1
  • Hypomethylation
  • Overexpression
  • Wilms tumor

ASJC Scopus subject areas

  • Cancer Research

Fingerprint Dive into the research topics of 'Hypomethylation and aberrant expression of the glioma pathogenesis-related 1 gene in Wilms tumors'. Together they form a unique fingerprint.

  • Cite this

    Chilukamarri, L., Hancock, A. L., Malik, S., Zabkiewicz, J., Baker, J. A., Greenhough, A., Dallosso, A. R., Huang, T. H. M., Royer-Pokora, B., Brown, K. W., & Malik, K. (2007). Hypomethylation and aberrant expression of the glioma pathogenesis-related 1 gene in Wilms tumors. Neoplasia, 9(11), 970-978. https://doi.org/10.1593/neo.07661