The genomic landscape of familial glioma.

TitleThe genomic landscape of familial glioma.
Publication TypeJournal Article
Year of Publication2023
AuthorsChoi, D-J, Armstrong, G, Lozzi, B, Vijayaraghavan, P, Plon, SE, Wong, TC, Boerwinkle, E, Muzny, DM, Chen, H-C, Gibbs, RA, Ostrom, QT, Melin, B, Deneen, B, Bondy, ML, Bainbridge, MN, Amos, CI, Barnholtz-Sloan, JS, Bernstein, JL, Claus, EB, Houlston, RS, Il'yasova, D, Jenkins, RB, Johansen, C, Lachance, D, Lai, R, Melin, BS, Merrell, RT, Olson, SH, Sadetzki, S, Schildkraut, J, Shete, S, Ambrose, JC, Arumugam, P, Bevers, R, Bleda, M, Boardman-Pretty, F, Boustred, CR, Brittain, H, Brown, MA, Caulfield, MJ, Chan, GC, Giess, A, Griffin, JN, Hamblin, A, Henderson, S, Hubbard, TJP, Jackson, R, Jones, LJ, Kasperaviciute, D, Kayikci, M, Kousathanas, A, Lahnstein, L, Lakey, A, Leigh, SEA, Leong, IUS, Lopez, FJ, Maleady-Crowe, F, McEntagart, M, Minneci, F, Mitchell, J, Moutsianas, L, Mueller, M, Murugaesu, N, Need, AC, O'Donovan, P, Odhams, CA, Patch, C, Perez-Gil, D, Pereira, MB, Pullinger, J, Rahim, T, Rendon, A, Rogers, T, Savage, K, Sawant, K, Scott, RH, Siddiq, A, Sieghart, A, Smith, SC, Sosinsky, A, Stuckey, A, Tanguy, M, Tavares, ALTaylor, Thomas, ERA, Thompson, SR, Tucci, A, Welland, MJ, Williams, E, Witkowska, K, Wood, SM, Zarowiecki, M
Corporate AuthorsGliogene Consortium, Genomics England Research Consortium
JournalSci Adv
Volume9
Issue17
Paginationeade2675
Date Published2023 Apr 28
ISSN2375-2548
KeywordsBrain Neoplasms, Calcium-Binding Proteins, DNA-Binding Proteins, Genetic Predisposition to Disease, Genomics, Glioma, Humans, Tumor Suppressor Proteins, Whole Genome Sequencing
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 ( = 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 , have profound impacts on proliferation. This study performs comprehensive surveillance of the genomic landscape of familial glioma.

DOI10.1126/sciadv.ade2675
Alternate JournalSci Adv
PubMed ID37115922
PubMed Central IDPMC10146888

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