Germline mutations in shelterin complex genes are associated with familial glioma Journal Article


Authors: Bainbridge, M. N.; Armstrong, G. N.; Gramatges, M. M.; Bertuch, A. A.; Jhangiani, S. N.; Doddapaneni, H.; Lewis, L.; Tombrello, J.; Tsavachidis, S.; Liu, Y.; Jalali, A.; Plon, S. E.; Lau, C. C.; Parsons, D. W.; Claus, E. B.; Barnholtz-Sloan, J.; Il'yasova, D.; Schildkraut, J.; Ali-Osman, F.; Sadetzki, S.; Johansen, C.; Houlston, R. S.; Jenkins, R. B.; LaChance, D.; Olson, S. H.; Bernstein, J. L.; Merrell, R. T.; Wrensch, M. R.; Walsh, K. M.; Davis, F. G.; Lai, R.; Shete, S.; Aldape, K.; Amos, C. I.; Thompson, P. A.; Muzny, D. M.; Gibbs, R. A.; Melin, B. S.; Bondy, M. L.
Article Title: Germline mutations in shelterin complex genes are associated with familial glioma
Abstract: 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. © The Author 2014. Published by Oxford University Press.
Keywords: adult; controlled study; aged; middle aged; unclassified drug; gene sequence; major clinical study; somatic mutation; glioma; protein localization; cancer susceptibility; protein; protein binding; genetic association; genetic variability; genotype; oligodendroglioma; dna binding; genetic predisposition; germline mutation; exome; telomere homeostasis; very elderly; human; male; female; priority journal; article; protein pot1; protein tpp1
Journal Title: JNCI: Journal of the National Cancer Institute
Volume: 107
Issue: 1
ISSN: 0027-8874
Publisher: Oxford University Press  
Date Published: 2015-01-01
Start Page: dju384
Language: English
DOI: 10.1093/jnci/dju384
PUBMED: 25482530
PROVIDER: scopus
PMCID: PMC4296199
DOI/URL:
Notes: Export Date: 2 July 2015 -- Source: Scopus
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MSK Authors
  1. Sara H Olson
    213 Olson
  2. Jonine L Bernstein
    104 Bernstein