TY - JOUR
T1 - Germline mutations in shelterin complex genes are associated with familial glioma
AU - Bainbridge, Matthew N.
AU - Armstrong, Georgina N.
AU - Gramatges, M. Monica
AU - Bertuch, Alison A.
AU - Jhangiani, Shalini N.
AU - Doddapaneni, Harsha
AU - Lewis, Lora
AU - Tombrello, Joseph
AU - Tsavachidis, Spyros
AU - Liu, Yanhong
AU - Jalali, Ali
AU - Plon, Sharon E.
AU - Lau, Ching C.
AU - Parsons, Donald W.
AU - Claus, Elizabeth B.
AU - Barnholtz-Sloan, Jill
AU - Il'yasova, Dora
AU - Schildkraut, Joellen
AU - Ali-Osman, Francis
AU - Sadetzki, Siegal
AU - Johansen, Christoffer
AU - Houlston, Richard S.
AU - Jenkins, Robert B.
AU - Lachance, Daniel
AU - Olson, Sara H.
AU - Bernstein, Jonine L.
AU - Merrell, Ryan T.
AU - Wrensch, Margaret R.
AU - Walsh, Kyle M.
AU - Davis, Faith G.
AU - Lai, Rose
AU - Shete, Sanjay
AU - Aldape, Kenneth
AU - Amos, Christopher I.
AU - Thompson, Patricia A.
AU - Muzny, Donna M.
AU - Gibbs, Richard A.
AU - Melin, Beatrice S.
AU - Bondy, Melissa L.
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health and the National Human Genome Research Institute, Bethesda, Maryland (R01CA119215, R01CA070917, R01CA52689, P50097257, R01CA126831, U54HG003273, P30CA125123, K23CA 158148, 5 R01CA138836, 5 P30 CA125123). Additional support was provided by the McNair Medical Institute, the Population Sciences Biorespository at Baylor College of Medicine, the American Brain Tumor Association, the St. Baldrick’s Foundation, and The National Brain Tumor Society.
Publisher Copyright:
© The Author 2014. Published by Oxford University Press.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
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U2 - 10.1093/jnci/dju384
DO - 10.1093/jnci/dju384
M3 - Article
C2 - 25515231
AN - SCOPUS:84930462553
SN - 0027-8874
VL - 107
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 1
M1 - dju384
ER -