Nav: Home

New molecular mechanism revealed for genetic mutations in aggressive cancer cells

October 11, 2016

Scientists at the University of Birmingham have described a previously-unknown molecular mechanism that could lead to the genetic mutations seen in certain types of aggressive cancer cells, involving a cell's own transcription machinery.

Genetic mutations are fundamental to the spread of cancer cells that form malignant tumours in the body. They are often caused by 'replication stress' within the cell, whereby DNA becomes damaged while it is duplicated. However, the underlying cause of this process has long been a mystery.

In a new study published today in Nature Communications, researchers reveal how replication stress (and subsequent genetic mutations) can be caused by an increase in activity of a cell's own transcription machinery.

The research shows that in cells with an activated version of the cancer-promoting gene (or 'oncogene') H-RasV12, the rate of transcription and protein production is dramatically increased. The resulting RNA can form unusual structures called 'R-loops' within the DNA of the cell, which in turn cause DNA damage and replication stress.

Although it was previously suspected that H-RasV12 caused increases in transcription, this study provides the first solid evidence of the mechanism, as well as the first description of the role of this oncogene in R-loop formation.

'This research is the first to show conclusively that an oncogene-induced boost in gene expression is enough to interfere with DNA replication,' says lead researcher Dr Eva Petermann, from the University of Birmingham's Institute of Cancer and Genomic Studies.

'Our findings help to create a new unified view of the roles of transcription and replication in the process of cancer cell mutations. This is a big step in basic cancer biology, and potentially opens up a whole new area of research into transcription proteins and replication stress.'

A better understanding of replication stress may help improve the efficacy and application of a number of new cancer drugs currently undergoing clinical trials, including AstraZeneca's ATR and Wee1 inhibitors.
-end-


University of Birmingham

Related Cancer Articles:

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
More Cancer News and Cancer Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Erasing The Stigma
Many of us either cope with mental illness or know someone who does. But we still have a hard time talking about it. This hour, TED speakers explore ways to push past — and even erase — the stigma. Guests include musician and comedian Jordan Raskopoulos, neuroscientist and psychiatrist Thomas Insel, psychiatrist Dixon Chibanda, anxiety and depression researcher Olivia Remes, and entrepreneur Sangu Delle.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...