During the process of examining brain tumors that carry mutations in their isocitrate dehydrogenase (IDH) genes, a team of scientists from the Broad Institute of MIT and Harvard have discovered a new biological mechanism that underlies cancer: genome misfolding.
In the brain tumors, the mutations in the IDH genes lead to unusual changes in the folding of the genome, stimulating changes in the insulators, which are key genomic locations that physically prevent genes in one area from interacting with and altering genes in another area.
"This is a totally new mechanism for causing cancer, and we think it will hold true not just in brain tumors, but in other forms of cancer," Bradley Bernstein, senior author of the study, said in a press release. "It is well established that cancer-causing genes can be abnormally activated by changes in their DNA sequence. But in this case, we find that a cancer-causing gene is switched on by a change in how the genome folds."
The scientists found that when insulators began to become disorganized in cancerous tumors due to hypermethylation in IDH genes that spread to other areas of the genome, a crucial growth factor gene became taken over by an always-on gene switch, leading to a dangerously powerful cancer-promoting process.
Prior to the study, IDH gene mutations were thought to be standard "housekeeping" genes as opposed to key drivers of cancer. Although these findings point to IDH gene mutations as a key component in cancerous growth through genome misfolding, further research will need to be conducted to pinpoint its role in other forms of cancer.
"A variety of other tumors carry IDH mutations, including forms of leukemia, colon cancer, bladder cancer, and many others," said Bernstein. "It will be very interesting to see how generally this applies beyond glioma."
The findings were published in the Dec. 23 issue of Nature.
