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

TitleGermline mutations in shelterin complex genes are associated with familial glioma.
Publication TypeJournal Article
Year of Publication2015
AuthorsBainbridge, MN, Armstrong, GN, M Gramatges, M, 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
Corporate AuthorsGliogene Consortium
JournalJ Natl Cancer Inst
Date Published2015 Jan
KeywordsAdult, Aged, Brain Neoplasms, Exome, Female, Genetic Predisposition to Disease, Germ-Line Mutation, Glioma, Humans, Male, Middle Aged, Oligodendroglioma, Pedigree, Telomere-Binding Proteins

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.

Alternate JournalJ. Natl. Cancer Inst.
PubMed ID25482530
PubMed Central IDPMC4296199
Grant List5 P30 CA125123 / CA / NCI NIH HHS / United States
R01CA126831 / CA / NCI NIH HHS / United States
R01CA070917 / CA / NCI NIH HHS / United States
U54HG003273 / HG / NHGRI NIH HHS / United States
P30CA125123 / CA / NCI NIH HHS / United States
P30 CA023108 / CA / NCI NIH HHS / United States
5 R01CA138836 / CA / NCI NIH HHS / United States
R01 CA138836 / CA / NCI NIH HHS / United States
P50 CA097257 / CA / NCI NIH HHS / United States
R01CA52689 / CA / NCI NIH HHS / United States
R01CA119215 / CA / NCI NIH HHS / United States
P50097257 / / PHS HHS / United States
K23CA158148 / CA / NCI NIH HHS / United States
R01 CA052689 / CA / NCI NIH HHS / United States

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