Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas.

摘要: BACKGROUND: Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II III) have highly variable clinical behavior that is not adequately predicted on basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty compounded by interobserver variability in diagnosis. Mutations IDH, TP53, ATRX codeletion chromosome arms 1p 19q (1p/19q codeletion) been implicated as clinically relevant markers gliomas. METHODS: We performed genomewide analyses 293 from adults, incorporating exome sequence, DNA copy number, methylation, messenger RNA expression, microRNA targeted protein expression. These data were integrated tested for correlation with outcomes. RESULTS: Unsupervised clustering mutations RNA, DNA-copy-number, DNA-methylation platforms uncovered concordant classification three robust, nonoverlapping, prognostically significant subtypes glioma captured more accurately 1p/19q, TP53 status than Patients who had an IDH mutation 1p/19q most favorable Their harbored CIC, FUBP1, NOTCH1, TERT promoter. Nearly all no (94%) inactivation (86%). large majority without genomic aberrations strikingly similar those found primary CONCLUSIONS: integration multiple delineated molecular classes Lower-grade either or carried a mutation. Most molecularly (Funded National Institutes Health.)