Frequent epigenetic inactivation of KIBRA, an upstream member of the salvador/warts/ hippo (SWH) tumor suppressor network, is associated with specific genetic event in B-cell acute lymphocytic leukemia

Victoria K. Hill, Thomas Dunwell, Daniel Catchpoole, Dietmar Krex, Anna T. Brini, Mike Griffiths, Charles Craddock, Eamonn R. Maher, Farida Latif

Research output: Contribution to journalArticle

Abstract

The WW-domain containing protein KIBRA has recently been identified as a new member of the Salvador/Warts/Hippo (SWH) pathway in Drosophila and is shown to act as a tumor suppressor gene in Drosophila. This pathway is conserved in humans and members of the pathway have been shown to act as tumor suppressor genes in mammalian systems. We determined the methylation status of the 5' CpG island associated with the KIBRA gene in human cancers. In a large panel of cancer cell lines representing common epithelial cancers KIBRA was unmethylated. But in pediatric acute lymphocytic leukemia (ALL) cell lines KIBRA showed frequent hypermethylation and silencing of gene expression, which could be reversed by treatment with 5-aza-2'-deoxycytidine. In ALL patient samples KIBRA was methylated in 70% B-ALL but was methylated in

Original languageEnglish
Pages (from-to)326-332
Number of pages7
JournalEpigenetics
Volume6
Issue number3
DOIs
Publication statusPublished - Mar 2011

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Keywords

  • ALL
  • ETV6/RUNX1 translocation
  • KIBRA
  • Methylation
  • SWH pathway

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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