Medical scientists have found a new form of mechanism leading to hereditary cancer susceptibility, demonstrating that minor changes in certain anti-cancer genes might work as magnets to draw altering “biochemical tags”.
The tags successfully switch these genes off as well as predispose families to a higher risk associated with the condition. The researchers, from the University of New South Wales (UNSW), consider that a minor spelling error affecting just one letter in the DNA sequence close to the beginning of the gene is actually what draws in the biochemical marking, named methylation. This methylation switches genes off, thus has specific influences on the DNA.
“Methylation sits on top of our DNA, and provides the instructions to turn the gene off,” pointed out Dr Megan Hitchins.
In one well studied cause of hereditary cancer, alterations in the cancer-prevention gene MLH1 are transferred from mother or father to children. This situation generates up to 80 percent risk of developing bowel cancer, uterine cancer and other malignancies.
On the other hand, a number of family members with hereditary cancer do not have spelling mistakes in MLH1, but alternatively possess methylation placed on the gene.
“When the methylation attaches to the MLH1 gene in these families, it causes it to be completely switched off and as a consequence cancer develops,” affirmed head of the adult cancer program at the Lowy Cancer Research Centre, Professor Robyn Ward. “But until now, we did not understand how these methylation tags were being passed from parent to child.”
In the study the researchers investigated three generations of a large family, who had experienced cancer at young age, but in whom no spelling mistakes characteristic for this kind of inherited cancer syndrome had been identified. Noticeably a number of family members from all generations had methylation tags on their gene.
“In this family, biochemical tags attached to the MLH1 gene were present in all three generations. This was intriguing since these markers are usually removed during the production of eggs and sperm. What we found was that a subtle change near the gene was acting like a magnet to attract methylation. So it was not the methylation itself that was being passed from parent to child, but rather the DNA change, and this acted as a methyl magnet,” Dr Megan Hitchins said.
The methylation had disappeared in the semen and ova and after that regenerated in every brand-new generation, the researchers explained.
Professor Robyn Ward said the study had specified the trigger of cancer in this family and it had provided new options for genetic diagnosis, counselling as well as early treatment in other families vulnerable to hereditary cancer.
The group is additionally studying the utilization of specific medications (Epigenetic Reversal Drugs) to remove the methylation in cancer, thus to switch the anti-cancer genes back on again. Later on these medicines might be administered in order to create a more specific method of cancer therapy and perhaps prevention.
Additional scientists linked to this research have been the Genetic Services of Western Australia and School of Paediatrics and Child Health, University of Western Australia.
The study on hereditary cancer was published in the primary international journal “Cancer Cell”.