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

  1. Michael D. Blough MSc1,2,
  2. Mohammad Al-Najjar BSc1,2,
  3. Charles Chesnelong MSc1,2,
  4. Carmen E. Binding BSc1,2,
  5. Alexandra D. Rogers BSc1,2,
  6. H. Artee Luchman PhD1,3,
  7. John J. Kelly MD, PhD1,3,
  8. Larry Fliegel PhD4,
  9. Olena Morozova MSc5,
  10. Stephen Yip MD, PhD5,
  11. Marco Marra PhD5,
  12. Samuel Weiss PhD3,6,
  13. Jennifer A. Chan MD2,7,
  14. J. Gregory Cairncross MD1,2,3,*

Article first published online: 20 JUN 2012

DOI: 10.1002/ana.23610

Issue

Annals of Neurology

Annals of Neurology

Volume 71, Issue 6, pages 845–849, June 2012

Additional Information

How to Cite

Blough, M. D., Al-Najjar, M., Chesnelong, C., Binding, C. E., Rogers, A. D., Luchman, H. A., Kelly, J. J., Fliegel, L., Morozova, O., Yip, S., Marra, M., Weiss, S., Chan, J. A. and Cairncross, J. G. (2012), DNA hypermethylation and 1p Loss silence NHE-1 in oligodendroglioma. Ann Neurol., 71: 845–849. doi: 10.1002/ana.23610

Author Information

  1. 1

    Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta

  2. 2

    Clark Smith Brain Tumour Centre, University of Calgary, Calgary, Alberta

  3. 3

    Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta

  4. 4

    Department of Biochemistry, University of Alberta, Edmonton, Alberta

  5. 5

    Genome Sciences Centre, University of British Columbia, Vancouver, British Columbia

  6. 6

    Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta

  7. 7

    Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada

*Foothills Medical Centre, 1403 29th St NW, Calgary, Alberta, T2N2T9, Canada

Publication History

  1. Issue published online: 20 JUN 2012
  2. Article first published online: 20 JUN 2012
  3. Accepted manuscript online: 14 APR 2012 09:44AM EST
  4. Manuscript Accepted: 6 APR 2012
  5. Manuscript Revised: 30 MAR 2012
  6. Manuscript Received: 9 MAR 2012

Funded by

  • Alberta Innovates-Health Solutions
  • Alberta Cancer Foundation
  • Canadian Institutes for Health Research
  • Brain Tumour Foundation of Canada

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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. Ann Neurol 2012;71:845–849

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