| Literature DB >> 25482530 |
Matthew N Bainbridge1, Georgina N Armstrong1, M Monica Gramatges1, Alison A Bertuch1, Shalini N Jhangiani1, Harsha Doddapaneni1, Lora Lewis1, Joseph Tombrello1, Spyros Tsavachidis1, Yanhong Liu1, Ali Jalali1, Sharon E Plon1, Ching C Lau1, Donald W Parsons1, Elizabeth B Claus1, Jill Barnholtz-Sloan1, Dora Il'yasova1, Joellen Schildkraut1, Francis Ali-Osman1, Siegal Sadetzki1, Christoffer Johansen1, Richard S Houlston1, Robert B Jenkins1, Daniel Lachance1, Sara H Olson1, Jonine L Bernstein1, Ryan T Merrell1, Margaret R Wrensch1, Kyle M Walsh1, Faith G Davis1, Rose Lai1, Sanjay Shete1, Kenneth Aldape1, Christopher I Amos1, Patricia A Thompson1, Donna M Muzny1, Richard A Gibbs1, Beatrice S Melin1, Melissa L Bondy1.
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.Entities:
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Year: 2014 PMID： 25482530 PMCID： PMC4296199 DOI： 10.1093/jnci/dju384
Source DB: PubMed Journal: J Natl Cancer Inst ISSN： 0027-8874 Impact factor: 11.816