Scholars@Duke

The genomic landscape of familial glioma.

Publication ,  Journal Article
Choi, 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 ...
Published in: Sci Adv
April 28, 2023
Published version (DOI) Link to item

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.

Duke Scholars

Joellen Martha Schildkraut
Author Joellen Martha Schildkraut Family Medicine and Community Health, Prevention Research
Dora Ilyasova
Author Dora Ilyasova Family Medicine and Community Health, Prevention Research
Quinn Ostrom
Author Quinn Ostrom Neurosurgery, Neuro-Oncology
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Published In

Sci Adv

DOI

10.1126/sciadv.ade2675

EISSN

2375-2548

Publication Date

April 28, 2023

Volume

9

Issue

17

Start / End Page

eade2675

Location

United States

Related Subject Headings

  • Whole Genome Sequencing
  • Tumor Suppressor Proteins
  • Humans
  • Glioma
  • Genomics
  • Genetic Predisposition to Disease
  • DNA-Binding Proteins
  • Calcium-Binding Proteins
  • Brain Neoplasms
 

Citation

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Choi, D.-J., Armstrong, G., Lozzi, B., Vijayaraghavan, P., Plon, S. E., Wong, T. C., … Zarowiecki, M. (2023). The genomic landscape of familial glioma. Sci Adv, 9(17), eade2675. https://doi.org/10.1126/sciadv.ade2675
Choi, Dong-Joo, Georgina Armstrong, Brittney Lozzi, Prashanth Vijayaraghavan, Sharon E. Plon, Terence C. Wong, Eric Boerwinkle, et al. “The genomic landscape of familial glioma.” Sci Adv 9, no. 17 (April 28, 2023): eade2675. https://doi.org/10.1126/sciadv.ade2675.
Choi D-J, Armstrong G, Lozzi B, Vijayaraghavan P, Plon SE, Wong TC, et al. The genomic landscape of familial glioma. Sci Adv. 2023 Apr 28;9(17):eade2675.
Choi, Dong-Joo, et al. “The genomic landscape of familial glioma.” Sci Adv, vol. 9, no. 17, Apr. 2023, p. eade2675. Pubmed, doi:10.1126/sciadv.ade2675.
Choi 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, Gliogene Consortium, Genomics England Research Consortium, 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, Taylor Tavares AL, Thomas ERA, Thompson SR, Tucci A, Welland MJ, Williams E, Witkowska K, Wood SM, Zarowiecki M. The genomic landscape of familial glioma. Sci Adv. 2023 Apr 28;9(17):eade2675.

Published In

Sci Adv

DOI

10.1126/sciadv.ade2675

EISSN

2375-2548

Publication Date

April 28, 2023

Volume

9

Issue

17

Start / End Page

eade2675

Location

United States

Related Subject Headings

  • Whole Genome Sequencing
  • Tumor Suppressor Proteins
  • Humans
  • Glioma
  • Genomics
  • Genetic Predisposition to Disease
  • DNA-Binding Proteins
  • Calcium-Binding Proteins
  • Brain Neoplasms