Retrospective analysis of molecular and immunohistochemical characterization of 381 primary brain tumors

Abstract

The classification of brain tumors has traditionally depended on microscopic examination of hematoxylin and eosin-stained tissue sections. The increased understanding of clinically relevant genetic alterations has led to the incorporation of molecular signatures as part of the diagnosis of brain malignancies. Advances in sequencing technologies have facilitated the use of next-generation sequencing (NGS) assays in clinical laboratories. We performed a retrospective analysis of sequencing results for 381 brain tumors tested by NGS at our institution using a validated, commercially available panel. The results of the NGS assay were analyzed in conjunction with the results of immunohistochemical stains. A genetic alteration was detected in approximately two thirds of the cases. The most commonly mutated genes were TP53 (37.2%), IDH1 (29.4%), PIK3CA (8%), PTEN (8%), and EGFR (7.5%). BRAF mutations were detected in 3% of the cases, including 50% of gangliogliomas and 20% of gliosarcomas. No mutations were detected in 6 medulloblastomas. PIK3CA and CTNNB1 mutations were detected in 1 rosette-forming glioneuronal tumor and 1 adamantinomatous craniopharyngioma, respectively. Approximately 23% of cases showed amplification of 1 or more of the genes included in the NGS panel. This analysis demonstrates the utility of NGS for detecting genetic alterations in brain tumors in the clinical setting.