@article{c52c75824c174b8b94ca4ab75a83b541,
title = "The genomic landscape of familial glioma",
abstract = "Glioma is a rare brain tumor with a poor prognosis. Familial glioma is a subset of glioma with a strong genetic predisposition that accounts for approximately 5% of glioma cases. We performed whole-genome sequencing on an exploratory cohort of 203 individuals from 189 families with a history of familial glioma and an additional validation cohort of 122 individuals from 115 families. We found significant enrichment of rare deleterious variants of seven genes in both cohorts, and the most significantly enriched gene was HERC2 (P = 0.0006). Furthermore, we identified rare noncoding variants in both cohorts that were predicted to affect transcription factor binding sites or cause cryptic splicing. Last, we selected a subset of discovered genes for validation by CRISPR knockdown screening and found that DMBT1, HP1BP3, and ZCH7B3 have profound impacts on proliferation. This study performs comprehensive surveillance of the genomic landscape of familial glioma.",
author = "{The Gliogene Consortium} and {Genomics England Research Consortium} and Choi, {Dong Joo} and Georgina Armstrong and Brittney Lozzi and Prashanth Vijayaraghavan and Plon, {Sharon E.} and Wong, {Terence C.} and Eric Boerwinkle and Muzny, {Donna M.} and Chen, {Hsiao Chi} and Gibbs, {Richard A.} and Ostrom, {Quinn T.} and Beatrice Melin and Benjamin Deneen and Bondy, {Melissa L.} and Bainbridge, {Matthew N.} and Amos, {Christopher I.} and Barnholtz-Sloan, {Jill S.} and Bernstein, {Jonine L.} and Claus, {Elizabeth B.} and Houlston, {Richard S.} and Dora Il'yasova and Jenkins, {Robert B.} and Christoffer Johansen and Daniel Lachance and Rose Lai and Melin, {Beatrice S.} and Merrell, {Ryan T.} and Olson, {Sara H.} and Siegal Sadetzki and Joellen Schildkraut and Sanjay Shete and Ambrose, {J. C.} and P. Arumugam and R. Bevers and M. Bleda and F. Boardman-Pretty and Boustred, {C. R.} and H. Brittain and Brown, {M. A.} and Caulfield, {M. J.} and Chan, {G. C.} and A. Giess and Griffin, {J. N.} and A. Hamblin and S. Henderson and Hubbard, {T. J.P.} and R. Jackson and Jones, {L. J.} and D. Kasperaviciute and M. Kayikci",
note = "Publisher Copyright: Copyright {\textcopyright} 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC)",
year = "2023",
month = apr,
day = "28",
doi = "10.1126/SCIADV.ADE2675",
language = "English (US)",
volume = "9",
journal = "Science Advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "17",
}