DNA hypermethylation and 1p Loss silence NHE-1 in oligodendroglioma.
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.
Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
Michael D
MD
Blough
Mohammad
M
Al-Najjar
Charles
C
Chesnelong
Carmen E
CE
Binding
Alexandra D
AD
Rogers
H Artee
HA
Luchman
John J
JJ
Kelly
Larry
L
Fliegel
Olena
O
Morozova
Stephen
S
Yip
Marco
M
Marra
Samuel
S
Weiss
Jennifer A
JA
Chan
J Gregory
JG
Cairncross
D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D019175:DNA Methylation; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009837:Oligodendroglioma / Q000235:genetics* / Q000473:pathology; D011522:Protons; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics*; D014407:Tumor Cells, Cultured
D011522:Protons; D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1