Mitochondrial DNA may hold key to early targeting of brain tumours

Hudson Institute research suggests that new ways to target a severe form of adult brain cancer in its early stages could lie in our mitochondrial DNA.

Glioblastoma multiforme (commonly known as Glioblastoma) is the most common form of brain cancer in adults, yet it has a devastatingly low five year survival rate of just 4.6 per cent.

In a new study, Professor Jus St John, head of the Mitochondrial Genetics Research Group together with former PhD student Dr Xin (Claire) Sun generated glioblastoma tumours from populations of human cells with varying levels of mitochondrial DNA.

They found that tumours grown from cells with fewer copies of mitochondrial DNA developed more slowly. The findings have been published in the journal Epigenetics & Chromatin.

For cells to function effectively, each cell type requires a specific number of mitochondrial DNA copies. In tumours, it appears that mitochondrial DNA copy number can regulate the levels of DNA methylation that, in turn, affect the expression of genes encoded by the cell’s other genome, nuclear DNA.

“We showed that tumours generated from cells with fewer copies of mitochondrial DNA took significantly longer to form and formed at lower rates than tumours from cells with normal levels of mitochondrial DNA copy number. This took place because the cells with fewer copies of mitochondrial DNA had very different patterns of DNA methylation, which is a process that controls the expression of our genes especially during development.” Prof St John said.

“The nuclear and mitochondrial genomes exist in synchrony to establish a cell’s genetic balance which enables the cell to adopt its specific characteristics. This ‘genetic balance’ between the nuclear and mitochondrial genomes is important to the development of tumours.”

Prof St John says the findings could lead to new methods to target glioblastoma in its early stages – but work needs to first be done to target only the mitochondrial DNA in tumour cells.

“Targeting the mitochondrial genome in early tumours could be an approach to prevent tumours developing into their fully-blown state,” Prof St. John explained.

“The next step is to develop a way to isolate and target mitochondrial DNA that is in tumour cells. We can’t realistically target all the mitochondrial DNA in the body, as it is in all of our cells and is necessary for our survival.”

What is mitochondrial DNA?

The mitochondrial genome houses genes that provide power for cells. It works in synchrony with the nuclear genome (which we know as our DNA).

The mitochondrial genome is an essential component of cell function and an individual’s survival, but it is also essential for tumour formation.

Facts

Brain cancer survival rates are low, and have not improved much in the past 30 years. Australians diagnosed with brain cancer had around a 25 per cent chance of surviving for five years from 2009 to 2013.

Glioblastoma is the most common form of brain cancer in adults, and has a five year survival rate of just 4.6 per cent.

In 2018, it’s estimated that brain cancer will be the 17th most commonly diagnosed cancer.

In 2018, it is estimated that 1,935 new cases of brain cancer will be diagnosed in Australia (1,135 males and 800 females).

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