title: MRI-localized biopsies reveal subtype-specific differences in molecular and cellular composition at the margins of glioblastoma.
abstract: Glioblastomas (GBMs) diffusely infiltrate the brain, making complete removal by surgical resection impossible. The mixture of neoplastic and nonneoplastic cells that remain after surgery form the biological context for adjuvant therapeutic intervention and recurrence. We performed RNA-sequencing (RNA-seq) and histological analysis on radiographically guided biopsies taken from different regions of GBM and showed that the tissue contained within the contrast-enhancing (CE) core of tumors have different cellular and molecular compositions compared with tissue from the nonenhancing (NE) margins of tumors. Comparisons with the The Cancer Genome Atlas dataset showed that the samples from CE regions resembled the proneural, classical, or mesenchymal subtypes of GBM, whereas the samples from the NE regions predominantly resembled the neural subtype. Computational deconvolution of the RNA-seq data revealed that contributions from nonneoplastic brain cells significantly influence the expression pattern in the NE samples. Gene ontology analysis showed that the cell type-specific expression patterns were functionally distinct and highly enriched in genes associated with the corresponding cell phenotypes. Comparing the RNA-seq data from the GBM samples to that of nonneoplastic brain revealed that the differentially expressed genes are distributed across multiple cell types. Notably, the patterns of cell type-specific alterations varied between the different GBM subtypes: the NE regions of proneural tumors were enriched in oligodendrocyte progenitor genes, whereas the NE regions of mesenchymal GBM were enriched in astrocytic and microglial genes. These subtype-specific patterns provide new insights into molecular and cellular composition of the infiltrative margins of GBM.
authors.affiliation: Departments of Neurological Surgery.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Gill
authors.affiliation: Pathology and Cell Biology.
authors.forename: David J
authors.initials: DJ
authors.lastname: Pisapia
authors.affiliation: Departments of Neurological Surgery.
authors.forename: Hani R
authors.initials: HR
authors.lastname: Malone
authors.affiliation: Departments of Neurological Surgery.
authors.forename: Hannah
authors.initials: H
authors.lastname: Goldstein
authors.affiliation: Pathology and Cell Biology.
authors.forename: Liang
authors.initials: L
authors.lastname: Lei
authors.affiliation: Departments of Neurological Surgery.
authors.forename: Adam
authors.initials: A
authors.lastname: Sonabend
authors.affiliation: Departments of Neurological Surgery.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Yun
authors.affiliation: Departments of Neurological Surgery.
authors.forename: Jorge
authors.initials: J
authors.lastname: Samanamud
authors.affiliation: Departments of Neurological Surgery.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Sims
authors.affiliation: Departments of Neurological Surgery.
authors.forename: Matei
authors.initials: M
authors.lastname: Banu
authors.affiliation: Pathology and Cell Biology.
authors.forename: Athanassios
authors.initials: A
authors.lastname: Dovas
authors.affiliation: Pathology and Cell Biology.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Teich
authors.affiliation: Departments of Neurological Surgery.
authors.forename: Sameer A
authors.initials: SA
authors.lastname: Sheth
authors.affiliation: Departments of Neurological Surgery.
authors.forename: Guy M
authors.initials: GM
authors.lastname: McKhann
authors.affiliation: Departments of Neurological Surgery.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Sisti
authors.affiliation: Departments of Neurological Surgery, pc561@columbia.edu jnb2@columbia.edu pas2182@columbia.edu.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Bruce
authors.affiliation: Systems Biology, and Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY 10032 pc561@columbia.edu jnb2@columbia.edu pas2182@columbia.edu.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Sims
authors.affiliation: Pathology and Cell Biology, pc561@columbia.edu jnb2@columbia.edu pas2182@columbia.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Canoll
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D003287:Contrast Media; D005260:Female; D005909:Glioblastoma / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D061705:Image-Guided Biopsy; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012334:RNA, Neoplasm / Q000235:genetics; D017423:Sequence Analysis, RNA; D059467:Transcriptome; D059016:Tumor Microenvironment
chemical_list: D003287:Contrast Media; D012334:RNA, Neoplasm
keywords: glioma; microenvironment; tumor heterogeneity
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