The genomic landscape of familial glioma
-
Published:2023-04-28
Issue:17
Volume:9
Page:
-
ISSN:2375-2548
-
Container-title:Science Advances
-
language:en
-
Short-container-title:Sci. Adv.
Author:
Choi Dong-Joo1ORCID, Armstrong Georgina2ORCID, Lozzi Brittney1, Vijayaraghavan Prashanth3, Plon Sharon E.4, Wong Terence C.3, Boerwinkle Eric5, Muzny Donna M.6ORCID, Chen Hsiao-Chi1ORCID, Gibbs Richard A.6ORCID, Ostrom Quinn T.7ORCID, Melin Beatrice8ORCID, Deneen Benjamin1ORCID, Bondy Melissa L.2ORCID, Bainbridge Matthew N.3ORCID, Amos Christopher I., Barnholtz-Sloan Jill S., Bernstein Jonine L., Claus Elizabeth B., Houlston Richard S., Il'yasova Dora, Jenkins Robert B., Johansen Christoffer, Lachance Daniel, Lai Rose, Melin Beatrice S., Merrell Ryan T., Olson Sara H., Sadetzki Siegal, Schildkraut Joellen, Shete Sanjay, Ambrose J. C., Arumugam P., Bevers R., Bleda M., Boardman-Pretty F., Boustred C. R., Brittain H., Brown M. A., Caulfield M. J., Chan G. C., Giess A., Griffin J. N., Hamblin A., Henderson S., Hubbard T. J. P., Jackson R., Jones L. J., Kasperaviciute D., Kayikci M., Kousathanas A., Lahnstein L., Lakey A., Leigh S. E. A., Leong I. U. S., Lopez F. J., Maleady-Crowe F., McEntagart M., Minneci F., Mitchell J., Moutsianas L., Mueller M., Murugaesu N., Need A. C., O'Donovan P., Odhams C. A., Patch C., Perez-Gil D., Pereira M. B., Pullinger J., Rahim T., Rendon A., Rogers T., Savage K., Sawant K., Scott R. H., Siddiq A., Sieghart A., Smith S. C., Sosinsky A., Stuckey A., Tanguy M., Taylor Tavares A. L., Thomas E. R. A., Thompson S. R., Tucci A., Welland M. J., Williams E., Witkowska K., Wood S. M., Zarowiecki M., ,
Affiliation:
1. Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA. 2. Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA. 3. Rady Children’s Institute for Genomic Medicine, San Diego, CA, USA. 4. Department of Pediatrics/Hematology-Oncology, Baylor College of Medicine, Houston, TX, USA. 5. The University of Texas Health Science Center School of Public Health, Houston, TX, USA. 6. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA. 7. Department of Neurosurgery, Duke University School of Medicine, Durham, NC, USA. 8. Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
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.
Publisher
American Association for the Advancement of Science (AAAS)
Subject
Multidisciplinary
Cited by
8 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献
|
|