There is a process called hypermethylation that includes the build up of chemical bonds on certain cancer-promoting genes and this process renders the cells cancerous. The reverse process called demethylation does the exact opposite and wipes off these chemical bonds from the gene. Up until recently it was thought that demethylation was a very good therapy for those suffering from cancer but John Hopkins scientists are now saying that demethylation may also trigger more than half of all cancers. Joseph Califano, M.D., professor of otolaryngology-head and neck surgery and oncology at John Hopkins and his team of scientists have found that by studying the tissue of normal and cancerous cells from the human mouth, nose and throat they can provide enough evidence to suggest that important regulators of gene activity occur both outside and inside the DNA in a cell’s nucleus.
“While cancer-causing and other mutations alter vital protein-making pathways by rewriting the gene’s DNA code, epigenetic changes affect genes without changing the code itself. The new studies tell us that such changes occur not only when methyl groups bond to a gene’s on-off switch, but also when they come unglued,” stated Califano.
When two cell lines of normal oral tissue were treated with 5-azacytidine (demethylation drug) the team collected a list of all the genes that were activated and compared this list with the genes that were ‘turned on’ in 49 head and neck cancer samples and 19 normal tissue samples. They found 106 genes that were activated by demethylation and they also discovered that there was another gene that was present within all 106. This gene is called BORIS and it is the master regulator that recruits other proteins to help the demethylation process. In simple terms the more BORIS that was present the more cancer expression there was.
The team concluded that we should try to invent a drug that involves 5-azacytidine and a BORIS blocker in order to reduce the effect of demethylation producing more cancer.
Link: http://www.sciencedaily.com/releases/2009/03/090324101759.htm
Photo (Joseph Califano) link: http://www.eastman.ucl.ac.uk/iaoo/founders/pics/califa1.gif
Student number 42045823
