Which Mutations Lead To Cancer?

Researchers have discovered that common cancerous mutations arise in specific promoter regions of your DNA, and that repair in this regions is inhibited which means they don't get repaired  

Mutations happen all the time, but most of them are either repaired or are relatively harmless. Scientists are still working out exactly which mutations are a danger and which aren't, and understanding exactly what types and where lead to cancer is really important if we want better diagnosis and treatment. 

All about promoters

A team from UNSW in Australia studied more than 20 million mutations in thousands of tumours and found that in a large number of cancer, particularly skin, mutations centred on promoter regions. These also weren't being properly repaired. Promoters are sequences of DNA that act as a signal for your cell's machinery - controlling how much of that gene is expressed and when. They're crucial to normal gene function and many genes are switched off by controlling their promoters. If something happens to these regions, then the cell loses control and certain genes are really bad news for cells if they're activated too much or at the wrong time. 

"What this research … tells us is that while the human body is pretty good at repairing itself, there are certain parts of our genome that are poorly repaired when we sustain damage from mutagens such as UV light and cigarette smoke"

A squamous cell carinoma. Credit: Ed Uthman

Why are promoter mutations so dangerous? 

The research revealed that when mutations happen in promoter regions the body is less effective at repairing them. This is because promoters are often covered with proteins that control gene expression, which seems to prevent repair mechanisms reaching the DNA sequence and fixing it in a process called nucleotide excision repair (NER). In organs like the skin which are particularly exposed to mutagens like UV light, this becomes a bigger problem. 

"Our study highlights the need for further research on the role of gene promoter mutations in cancer development. This may ultimately help doctors to determine why certain cancers develop, enabling them to diagnose cancer earlier and select more tailored treatment therapies for patients"

A win for big data

The study is another 'win' for big data, using publicly available information and revealing new information from existing studies. Cancer is obviously a complex disease which isn't caused by promoter mutations alone, but the finding reinforces the need to study such mutations further. If we could better understand exactly why these aren't being repaired properly, we might be able to develop drugs to increase repair for example. 

"The findings are all the more impressive because they were uncovered using existing and publicly available ‘big data’, simply by asking the right questions. We didn't need to spend time and money recruiting patients, investigating their cancers and sequencing their cancer genomes. All of this data was available to researchers on public data sharing platforms"

Read more at ScienceAlert