Scientists may be a step closer to new cancer treatments after discovering thousands of genetic mutations that increase the risk of developing the disease.
Experts have long known that many cases are linked to problems with a gene called BAP1, also known as the “tumor protection gene,” which causes it to malfunction and fuel cancer growth.
But until now they were unsure what specific changes they should be aware of.
Now, British researchers have an answer after discovering more than 5,000 harmful flaws that can disrupt its protective effects.
They also found that about a fifth of these possible changes were caused by pathogens such as viruses, which significantly increase the risk of developing cancer of the eyes, lining of the lungs, brain, skin and even kidney.
Until now, experts were unsure of what specific genetic changes to look for in the “tumour protection” gene BAP1 that cause it to malfunction and promote cancer growth. But UK researchers have now discovered more than 5,000 harmful changes to the protein’s DNA that can disrupt its protective effects. Pictured here, researchers at the Wellcome Sanger Institute in Cambridgeshire
They found that about a fifth of these possible changes were caused by pathogens, significantly increasing the risk of developing cancer of the eyes, lung lining, brain, skin and even kidney.
In what could be welcome news for thousands of Britons at risk of the disease, scientists said the discovery could help patients get targeted treatments more quickly and open the door to the development of new drugs.
Professor Clare Turnbull, a cancer genetics expert at The Institute of Cancer Research in London and consultant in clinical cancer genetics at the Royal Marsden NHS Foundation Trust, said: “This research could mean more accurate interpretation of genetic tests, earlier diagnoses and better outcomes for patients and their families.”
Dr Andrew Waters, an expert in cancer gene mutations at the Wellcome Sanger Institute, added: ‘Previous approaches to studying how variants affect gene function have been on a very small scale or excluded important contexts that may contribute to how they behave.
‘Our approach provides a true picture of genetic behaviour, allowing for broader and more complex studies of genetic variation.
“This opens up new possibilities for understanding how these changes drive disease.”
Within the framework of the research, scientists from the Wellcome Sanger Institute, the Institute of Cancer Research, Londonand the University of Cambridge 18,108 DNA changes in the BAP1 gene were analyzed.
In a process scientifically known as “saturation genome editing,” they artificially altered the genetic code of human cells grown in a dish, identifying 5,665 of these changes as harmful.
People carrying these harmful variants of the BAP1 gene are ten percent more likely to be diagnosed with cancer than the general population.
Writing in the diary, Genetics of natureThe researchers also found that people with harmful BAP1 variants have elevated levels of IGF-1 in their blood, a hormone linked to both cancer growth and brain development.
Even people without cancer showed these elevated levels, suggesting that IGF-1 could be a target for new treatments to delay or prevent certain types of cancer, they added.
The discovery also opens the door to the development of new drugs that could inhibit these harmful effects, potentially slowing or preventing the progression of certain types of cancer, they said.
Early detection of these variants through genetic testing can also guide preventive measures and improve treatment efficacy.
Dr David Adams, senior author of the study from the Wellcome Sanger Institute, said: ‘We want to ensure that life-saving genetic knowledge is accessible and relevant to all people, regardless of their ancestry.
‘Our goal is to apply this technique to a broader range of genes, potentially covering the entire human genome in the next decade with the Atlas of Variant Effects.’
The BAP1 protein acts as a powerful tumor suppressor in the body, protecting against cancer of the eyes, lining of the lungs, brain, skin and kidney.
Inherited variants that alter the protein can increase the risk of developing these cancers by up to 50 percent.
Most BAP1-related cancers tend to be more aggressive and develop earlier in life, research shows.
At the same time, several studies have reported that patients with a BAP1 mutation have a seven-fold higher overall survival rate than those without a genetic predisposition.
