MRI-localized biopsies reveal subtype-specific differences in molecular and cellular composition at the margins of glioblastoma.

TitleMRI-localized biopsies reveal subtype-specific differences in molecular and cellular composition at the margins of glioblastoma.
Publication TypeJournal Article
Year of Publication2014
AuthorsGill BJ, Pisapia DJ, Malone HR, Goldstein H, Lei L, Sonabend A, Yun J, Samanamud J, Sims JS, Banu M, Dovas A, Teich AF, Sheth SA, McKhann GM, Sisti MB, Bruce JN, Sims PA, Canoll P
JournalProc Natl Acad Sci U S A
Volume111
Issue34
Pagination12550-5
Date Published2014 Aug 26
ISSN1091-6490
KeywordsAdult, Aged, Aged, 80 and over, Brain Neoplasms, Contrast Media, Female, Glioblastoma, Humans, Image-Guided Biopsy, Magnetic Resonance Imaging, Male, Middle Aged, RNA, Neoplasm, Sequence Analysis, RNA, Transcriptome, Tumor Microenvironment
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.

DOI10.1073/pnas.1405839111
Alternate JournalProc Natl Acad Sci U S A
PubMed ID25114226
Grant List1K01EB016071 / EB / NIBIB NIH HHS / United States
1R01NS066955 / NS / NINDS NIH HHS / United States
Related Faculty: 
David Pisapia, M.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700