DNA hypermethylation and 1p Loss silence NHE-1 in oligodendroglioma

Ann Neurol. 2012 Jun;71(6):845-9. doi: 10.1002/ana.23610.

Abstract

Oligodendroglioma is characterized by mutations of IDH and CIC, 1p/19q loss, and slow growth. We found that NHE-1 on 1p is silenced in oligodendrogliomas secondary to IDH-associated hypermethylation and 1p allelic loss. Silencing lowers intracellular pH and attenuates acid load recovery in oligodendroglioma cells. Others have shown that rapid tumor growth cannot occur without NHE-1-mediated neutralization of the acidosis generated by the Warburg glycolytic shift. Our findings show for the first time that the pH regulator NHE-1 can be silenced in a human cancer and also suggest that pH deregulation may contribute to the distinctive biology of human oligodendroglioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 1 / genetics*
  • DNA Methylation*
  • Humans
  • Mutation / genetics*
  • Oligodendroglioma / genetics*
  • Oligodendroglioma / pathology
  • Protons
  • Sodium-Hydrogen Exchangers / genetics*
  • Tumor Cells, Cultured

Substances

  • Protons
  • Sodium-Hydrogen Exchangers
  • growth factor-activatable Na-H exchanger NHE-1