Abstract

Significance Molecular analysis of surgically resected glioblastomas (GBM) samples has uncovered phenotypically and clinically distinct tumor subtypes. However, little is known about the molecular features of the glioma margins that are left behind after surgery. To address this key issue, we performed RNA-sequencing (RNA-seq) and histological analysis on MRI-guided biopsies from the contrast-enhancing core and nonenhancing margins of GBM. Computational deconvolution of the RNA-seq data revealed that cellular composition, including nonneoplastic cells, is a major determinant of the expression patterns at the margins of GBM. The different GBM subtypes show distinct expression patterns that relate the contrast enhancing centers to the nonenhancing margins of tumors. Understanding these patterns may provide a means to infer the molecular and cellular features of residual disease.