The genomic landscape of familial glioma

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 var-iants of seven genes in both cohorts, and the most significantly enriched gene was HERC2 (P = 0.0006). Further-more, 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.

Automated summary

This study conducted comprehensive surveillance of the genomic landscape of familial glioma and identified significant enrichment of rare deleterious variants in seven genes, with HERC2 being the most significantly enriched gene. Rare noncoding variants that may affect transcription factor binding sites or cause cryptic splicing were also found. Additionally, validation experiments revealed the significant impacts of DMBT1, HP1BP3, and ZCH7B3 genes on proliferation.