A “spelling mistake” in a DNA sequence can trigger a process that switches a crucial anti-cancer gene off, thereby boosting the risk of cancer developing, researchers have found.
In a paper published in the journal Cancer Cell, scientists from the University of NSW report on a study of three generations in a family with a predisposition to early bowel or uterine cancer.
The researchers wanted to understand what was causing methylation — a natural process that normally helps control which genes are expressed and which are not — to switch off a gene called MLH1, which is supposed to help prevent cancer developing.
“What we found was the family didn’t have a sequence change within the gene but they had a sequence change in front of the gene,” said study co-leader Dr Megan Hitchins from UNSW’s Lowy Cancer Research Centre.
“Literally one letter of the text in the front of the gene was swapped for another – just like a typo. These typos are passed from one generation to the next.”
The typo acted as a biochemical tag and attracted methylation to a certain spot where the anti-cancer gene was sitting, she said.
“It acted as a magnet, to attract this chemical that switches the gene off.”
The breakthrough could help identify other families at increased risk or even pave the way for drugs that stop methylation occurring and switch the anti-cancer genes back on, said Dr Hitchins.
Professor Bruce Armstrong, a bowel cancer expert from the University of Sydney’s School of Public Health said the research represented “an important, novel finding.”
“One could imagine a situation where you could target the methylation for the relevant region of the gene, even though you can’t actually change the genetic character,” said Professor Armstrong, who was not involved in the study.
“There could be some important discoveries down the track to reduce susceptibility or improve the prospect of success for treating people who have developed cancers as a consequence of this inherited characteristic.”