Germline mutations in shelterin complex genes are associated with familial glioma.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Bainbridge, MN; Armstrong, GN; Gramatges, MM; Bertuch, AA; Jhangiani, SN; Doddapaneni, H; Lewis, L; Tombrello, J; Tsavachidis, S; Liu, Y; Jalali, A; Plon, SE; Lau, CC; Parsons, DW; Claus, EB; Barnholtz-Sloan, J; Il'yasova, D; Schildkraut, J; Ali-Osman, F; Sadetzki, S; Johansen, C; Houlston, RS; Jenkins, RB; Lachance, D; Olson, SH; Bernstein, JL; Merrell, RT; Wrensch, MR; Walsh, KM; Davis, FG; Lai, R; Shete, S; Aldape, K; Amos, CI; Thompson, PA; Muzny, DM; Gibbs, RA; Melin, BS; Bondy, ML; Gliogene Consortium,

Published Date

  • January 2015

Published In

Volume / Issue

  • 107 / 1

Start / End Page

  • 384 -

PubMed ID

  • 25482530

Pubmed Central ID

  • PMC4296199

Electronic International Standard Serial Number (EISSN)

  • 1460-2105

Digital Object Identifier (DOI)

  • 10.1093/jnci/dju384


  • eng

Conference Location

  • United States