A â€œspelling mistakeâ€ 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 â€” a natural process that normally helps control which genes are expressed and which are not â€” to switch off a gene called MLH1, which is supposed to help prevent cancer developing.
â€œWhat we found was the family didnâ€™t have a sequence change within the gene but they had a sequence change in front of the gene,â€ said study co-leader Dr Megan Hitchins from UNSWâ€™s Lowy Cancer Research Centre.
â€œLiterally one letter of the text in the front of the gene was swapped for another â€“ just like a typo. These typos are passed from one generation to the next.â€
The typo acted as a biochemical tag and attracted methylation to a certain spot where the anti-cancer gene was sitting, she said.
â€œIt acted as a magnet, to attract this chemical that switches the gene off.â€
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 Sydneyâ€™s School of Public Health said the research represented â€œan important, novel finding.â€
â€œOne could imagine a situation where you could target the methylation for the relevant region of the gene, even though you canâ€™t actually change the genetic character,â€ said Professor Armstrong, who was not involved in the study.
â€œThere 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.â€