Epigenetics makes cancer cell "lean mean machine"

Researchers led by scientists from the Garvan Institute of Medical Research in Sydney have found some surprises in the epigenome of prostate cancer.

They found vast regions of the genome are silenced, more than previously expected, allowing the cancer cell to focus on proliferation to the exclusion of other functions.

Project leader Professor Susan Clark describes the typical cancer cell as a ‘lean mean machine’. “Epigenetic changes reduce the available genome to a point where only the genes that promote cell proliferation are accessible in the cancer cell,” she said in a release.

“We can see that the epigenome is remodelled in a very consistent and precise way, effectively swamping the expression of any gene that goes against the cancer cell’s interests.

“The swamping encompasses tumour suppressor genes, and all the neighbouring genes around them, as well as non-coding RNA, intergenic regions and microRNAs. Only those genes essential for growth activation are allowed to be active, while all the genes and regions that apply brakes are inactivated,” she said.

“The map tells us that the tumour cell is very different from the healthy cell. It also tells us that it works in a programmed rather than a random way, and that it targets a significant part of the genome, rather than just single genes.

“It tells us that treating cancer will be far more complex than we imagined, as it will first involve understanding and reversing epigenetic change.”

The paper, published today in Nature Cell Biology details the method used to create the epigenomic map, which was a three year project involving the development of novel bioinformatics and analysis techniques.

According to Clark, epigenetics will be crucial to understanding the behaviour of cancer cells as well as combating them.

“Now that we have a prostate cancer epigenome map, our next step will be to understand the mechanism that’s driving the chromatin reduction, or genome reduction, within these ‘lean mean machines’. In other words, what’s the link between the genetics and the epigenetics?”

The study involved researchers from the Garvan Instiitute, Emory University and the Atlanta VA Medical Center in Atlanta, U.S., the Walter and Eliza Hall Institute of Medical Research and the University of New South Wales.