Glioblastoma tumors exhibit more cellular diversity than previously thought

Glioblastoma is the most common and most aggressive form of brain cancer in adults. An exciting new study has characterized the cellular diversity in glioblastoma tumors from patients. This may pave the way for the development of new treatments.

"Glioblastoma is an incurable disease. There are existing therapies that may target 99% of the cells, but the tumor always comes back. Understanding the cellular landscape can provide a blueprint for identifying new therapies that target each of the various subpopulations of cancer cells, and ultimately help us tailor therapy to individual patient tumors," said co-senior author Bradley Bernstein, MD, PhD, professor of pathology at Massachusetts General Hospital and Harvard Medical School in Cambridge, Massachusetts.

Glioblastomas are classified into 1 of 4 cancer subtypes based on the predominant pattern of gene expression. Previous studies of glioblastoma looked at the average expression of genes across millions of cells combined together in a single sample.

The cells within a tumor are not homogenous, and researchers have suspected that this diversity may contribute to drug resistance and disease recurrence. Until now, it had been difficult to study the extent of this diversity.

A new approach called single-cell transcriptomics allowed researchers to look at gene expression patterns in 430 individual cells from five different patients with primary glioblastoma. Examining the gene expression patterns of many individual cells, one at a time, produced a detailed picture of the cellular composition of the tumors. The patterns of gene expression varied from cell to cell. Each glioblastoma contained individual cells from multiple cancer sub-types, and the distribution of these cells varied from tumor to tumor.

The study also found that the cancer cells in these tumors exist in many states. Some are stem-cell-like, suggesting they may play a role in tumor regeneration even after therapy. Others are more mature, differentiated cancer cells that make up the bulk of the tumor. Many cells exist on a spectrum between these states. Existing treatments target the most prevalent cells in a tumor and may miss some of these subpopulations.

"To focus on the aspects of heterogeneity that we thought could be clinically relevant, we looked primarily for distinct cell states, and found multiple subpopulations in each tumor. Clinically, what this means is that we might need to treat each tumor based on the complement of cellular subtypes it contains—not just the most prevalent one," said co-senior author Aviv Regev, PhD, director of the Klarman Cell Observatory and an associate professor at MIT.

This study was published online in Science Express (doi:10.1126/science.1254257).

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