A study analysing brain tumour genomics on a single-cell level has found evidence that cancer stem cells fuel the growth of oligodendrogliomas, a slow-growing but incurable form of brain cancer.

In their paper receiving advance online publication in Nature, a team led by investigators at Massachusetts General Hospital (MGH) and the Broad Institute of MIT and Harvard identifies for the first time cancer stem cells and their differentiated progeny in human brain tumour samples.

"Our work strongly supports that cancer stem cells are the main source of growth in these tumours and, as such, should be considered promising targets for treatment," says Mario Suvà, MD, PhD, of the MGH Department of Pathology, co-senior author of the Nature paper.

It has become clear that cancer stem cells — cells within tumours that exhibit stem cell characteristics and can differentiate into other specialized types of cancer cells — have a role in the progression and treatment resistance of several types of tumours, most prominently blood system tumours like leukaemia.

Several studies have supported a role for cancer stem cells in the aggressive brain tumours called glioblastoma, but those studies involved inducing human tumours to grow in mice, and as such their relevance to cancer in humans has been questioned.

To more accurately reflect the mechanisms driving oligodendrogliomas, the researchers used RNA sequencing to study directly, on a single-cell level, gene expression in samples from six early-stage human tumours.

Their analysis of more than 4,000 individual tumour cells, the largest effort to date in brain tumours, finds three developmental categories of cancer cells — one resembling neural stem cells and two characterised by sets of genes indicting paths towards differentiation.

The authors then observed that only a subset of cancer stem cells in each patient was showing signs of proliferation, while all other cancer cells were not.

Importantly, these three developmental signatures were found in distinct genetic clones — cells with identical patterns of genetic mutations — of tumour cells.

"Finding that different subclones within tumours show the same developmental patterns suggests that developmental programmes — whether in stem cells or differentiated cancer cells — set the context within which genetic evolution of oligodendroglioma occurs, which is key to supporting the cancer stem cell model," says Suvà, who is an assistant professor of Pathology at Harvard Medical School, an investigator with the MGH Center for Cancer Research, and an associate member of the Broad Institute.

"Trying to understand as much as we can about genetic versus non-genetic determinants of tumour organisation is key to our understanding of tumour propagation and to the design of new therapies. Our work suggests that targeting a specific stem cell phenotype, for example with immunotherapies, could be beneficial in patients with oligodendroglioma."

Source: Massachusetts General Hospital