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

Blough, Michael D; Al-Najjar, Mohammad; Chesnelong, Charles; Binding, Carmen E; Rogers, Alexandra D; Luchman, H Artee; Kelly, John J; Fliegel, Larry et al. · Ann Neurol · 2012

basic_science · Level V

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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.

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