DNA hypermethylation and 1p Loss silence NHE-1 in oligodendroglioma.
|Authors||Blough MD, Al-Najjar M, Chesnelong C, Binding CE, Rogers AD, Luchman HA, Kelly JJ, Fliegel L, Morozova O, Yip S, Marra M, Weiss S, Chan JA & Cairncross JG.|
|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.|
|Journal Name and Citation||
Ann Neurol. 2012 Jun;71(6):845-9.
|Date of Publication||2012/06/01|