Scientists find genetic mutation linked to aggressive brain cancer

13 Jun

Genetic errors have been identified as leading to a rare but aggressive form of brain cancer known as oligodendroglioma.

[anatomical illustration of the brain]
Errors were found in a gene that has a key role in the formation of the embryonic brain.

Researchers at the UK’s Institute of Cancer Research (ICR) in London collaborated with laboratories in France and Canada to compare the genetic sequence of 134 oligodendrogliomas with the DNA of healthy cells.

Their main finding was that errors in a gene known as TCF12 are associated with the more aggressive anaplastic oligodendrogliomas, and these results are published in the journal Nature Communications.

Mutations in the gene were found in 7.5% of anaplastic oligodendrogliomas.

The researchers found that this subset of cancers grew more rapidly, and in other ways seemed more aggressive, than those in which this gene was intact.

As introduced by the researched paper, anaplastic oligodendroglioma are “rare primary brain tumors that are generally incurable,” with a highly variable overall prognosis and few treatment targets identified.

Richard Houlston, professor of molecular and population genetics at ICR, says:

“Our in-depth study has set out many of the genetic defects that cause this rare but highly aggressive form of brain cancer – including identifying a gene mutation that appears in particularly fast-growing forms.”

Prof. Houlston adds:

“Anaplastic oligodendrogliomas are difficult to remove by surgery and don’t respond well to other forms of treatment.

We hope this new information might be used to discover new targeted therapies, offering patients a better chance at survival from this aggressive cancer.”

Genetic connection to metastatic tumor behavior

The researchers explain that TCF12 is the genetic code for a protein that binds to DNA and controls the activity of other genes.

Mutations in the gene were found to render the protein less able to bind to DNA, in turn reducing activity of other key genes, including one already associated with cancer spread.

The DNA sequence of 51 tumors was scanned initially and then the researchers looked for TCF12 mutations in an additional group of 83.

They also discovered errors in a gene known as IDH1 in 78% of the tumors, giving confirmation of an earlier scan of the data.

The hope for such science is that understanding genetic faults behind anaplastic oligodendrogliomas could allow the development of personalized therapies.

Finding consistencies with a more aggressive tumor expression, the scientists profiled the features of the tumors with the TCF12 mutation compared with those without the genetic error.

Findings included a greater extent of necrosis, higher mitotic index (a measure of the proportion of cells undergoing division and so proliferating) and staining differences seen under the microscope.

To the best of the researchers’ knowledge, their study represents the largest sequencing study of anaplastic oligodendroglioma done to date, although further work would be needed to increase the power of associations.

Written by Markus MacGill