Germline mutations in shelterin complex genes are associated with familial glioma

Matthew N. Bainbridge, Georgina N. Armstrong, M. Monica Gramatges, Alison A. Bertuch, Shalini N. Jhangiani, Harsha Doddapaneni, Lora Lewis, Joseph Tombrello, Spyros Tsavachidis, Yanhong Liu, Ali Jalali, Sharon E. Plon, Ching C. Lau, Donald W. Parsons, Elizabeth B. Claus, Jill Barnholtz-Sloan, Dora Il'yasova, Joellen Schildkraut, Francis Ali-Osman, Siegal SadetzkiChristoffer Johansen, Richard S. Houlston, Robert B. Jenkins, Daniel Lachance, Sara H. Olson, Jonine L. Bernstein, Ryan T. Merrell, Margaret R. Wrensch, Kyle M. Walsh, Faith G. Davis, Rose Lai, Sanjay Shete, Kenneth Aldape, Christopher I. Amos, Patricia A. Thompson, Donna M. Muzny, Richard A. Gibbs, Beatrice S. Melin, Melissa L. Bondy

Research output: Contribution to journalArticlepeer-review

116 Scopus citations


Gliomas are the most common brain tumor, with several histological subtypes of various malignancy grade. The genetic contribution to familial glioma is not well understood. Using whole exome sequencing of 90 individuals from 55 families, we identified two families with mutations in POT1 (p.G95C, p.E450X), a member of the telomere shelterin complex, shared by both affected individuals in each family and predicted to impact DNA binding and TPP1 binding, respectively. Validation in a separate cohort of 264 individuals from 246 families identified an additional mutation in POT1 (p.D617Efs), also predicted to disrupt TPP1 binding. All families with POT1 mutations had affected members with oligodendroglioma, a specific subtype of glioma more sensitive to irradiation. These findings are important for understanding the origin of glioma and could have importance for the future diagnostics and treatment of glioma.

Original languageEnglish (US)
Article numberdju384
JournalJournal of the National Cancer Institute
Issue number1
StatePublished - Jan 1 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Germline mutations in shelterin complex genes are associated with familial glioma'. Together they form a unique fingerprint.

Cite this