Siyuan Zheng, Kristin Alfaro-Munoz, Wei Wei, Xiaojing Wang, Fang Wang, Agda Karina Eterovic, Kenna R Mills Shaw, Funda Meric-Bernstam, Gregory N Fuller, Ken Chen, Roel G Verhaak, Gordon B Mills, WK Alfred Yung, Shiao-Pei Weathers, John F de Groot
Malignant gliomas are a group of intracranial cancers associated with disproportionately high mortality and morbidity. Here, we report ultradeep targeted sequencing of a prospective cohort of 237 tumors from 234 patients consisting of both glioblastoma (GBM) and lower-grade glioma (LGG) using our customized gene panels. We identified 2,485 somatic mutations, including single-nucleotide substitutions and small indels, using a validated in-house protocol. Sixty-one percent of the mutations were contributed by 12 hypermutators. The hypermutators were enriched for recurrent tumors and had comparable outcomes, and most were associated with temozolomide exposure. TP53 was the most frequently mutated gene in our cohort, followed by IDH1 and EGFR. We detected at least one EGFR mutation in 23% of LGGs, which was significantly higher than 6% seen in The Cancer Genome Atlas, a pattern that can be …
