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

被引：24

作者：

Blough, Michael D. ^{[2
]}

Al-Najjar, Mohammad ^{[2
]}

Chesnelong, Charles ^{[2
]}

Binding, Carmen E. ^{[2
]}

Rogers, Alexandra D. ^{[2
]}

Luchman, H. Artee ^{[3
]}

Kelly, John J. ^{[3
]}

Fliegel, Larry ^{[4
]}

Morozova, Olena ^{[5
]}

Yip, Stephen ^{[5
]}

Marra, Marco ^{[5
]}

Weiss, Samuel ^{[3
,6
]}

Chan, Jennifer A. ^{[2
,7
]}

Cairncross, J. Gregory ^{[1
,2
,3
]}

机构：

[1] Univ Calgary, Dept Clin Neurosci, Foothills Med Ctr, Calgary, AB T2N 2T9, Canada

[2] Univ Calgary, Clark Smith Brain Tumour Ctr, Calgary, AB T2N 2T9, Canada

[3] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB T2N 2T9, Canada

[4] Univ Alberta, Dept Biochem, Edmonton, AB, Canada

[5] Univ British Columbia, Genome Sci Ctr, Vancouver, BC V5Z 1M9, Canada

[6] Univ Calgary, Dept Cell Biol & Anat, Calgary, AB T2N 2T9, Canada

[7] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB T2N 2T9, Canada

来源：

ANNALS OF NEUROLOGY | 2012年 / 71卷 / 06期

关键词：

INTRACELLULAR PH REGULATION; NA+/H+ EXCHANGER; MUTATIONS; IDH1;

D O I：

10.1002/ana.23610

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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-1mediated 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. Ann Neurol 2012;71:845849

引用

页码：845 / 849

页数：5

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