The study, published Oct. 2 in Nature, was led by UChicago Prof. Chuan He and University of Texas Health Science Centre at San Antonio Prof. Mingjiang Xu, who found that RNA mediates how DNA is packaged and shed into your cells through the gene TET2. The title of the paper is “RNA TET2 oxides m5C to regulate chromatin state and leukaemogenesis.”
It’s also likely that this pathway explains a longstanding mystery about why so many cancers and other disorders involve TET2-related mutations, and provides a new set of potential targets for therapy, Hackett said.
A silver bullet:
This discovery is the most exciting thing to cancer researchers because it opens up a whole new set of targets for cancer drugs.
“We hope that we can get from this a silver bullet to specifically eradicate only cancer cells by blocking this particular pathway that is activated due to TET2 or IDH loss, and we are trying to create a company that will be able to create such a drug,” said He, who is working with UChicago’s Polsky Centre for Entrepreneurship and Innovation, also at the Cancer Centre, to establish such a company.
However, we also know that TET2 mutations produce effects beyond cancer. A slight number of all adults older than 70 have TET2 mutations and carry a greater risk of heart disease, stroke, diabetes and other inflammatory conditions called CHIP.
While these patients don’t yet have cancer, these patients have TET2 mutant blood cells, and can be treated,” said Caner Saygin, an oncologist and assistant professor of medicine at the University of Chicago Medicine who treats CHIP patients and works with the He lab on several projects.
“What we saw was that the TET2 mutant cells were more inflammatory, and when these cells circulate they increase risk for things like heart, liver, and kidney diseases.”
Previously we knew one type of RNA methylation called m6A affects gene expression, its placement and removal affect the packaging of chromatin that tells which stretches of DNA are to be translated into reality.
However, if m5C is also in this category then that indicates this is a more general mechanism for controlling chromatin and gene expression, and more.
“It shows RNA modification on chromatin as a major mechanism for the regulation of chromatin and gene transcription.”
Reference:Â University of Chicago. Scientists decode key mutation in many cancers, pointing to expanded role of RNA in human gene expressionÂ
