Science: Uncovering a molecular mechanism by which non-coding single nucleotide polymorphisms drive human gliomagenesis

Scientists from Mount Sinai Hospital and other institutions have identified important clues for the prevention and treatment of human gliomas through research, and the relevant research results may provide new ideas and perspectives
for revealing the biological changes behind the occurrence of gliomas.

Establishing a causal link between genetic polymorphisms and cancer risk is challenging
for scientists.
Recently, in a research report published in the international journal Science entitled "A noncoding single-nucleotide polymorphism at 8q24 drives IDH1 -mutant glioma formation", scientists from Mount Sinai Hospital and other institutions have identified important clues for the prevention and treatment of human gliomas through research.
Relevant research results may provide new ideas and perspectives
for revealing the biological changes behind glioma.

The researchers found that animal models carrying DNA changes with germline alterations rs55705857 developed gliomas more frequently and in half the time to develop than those that did not, and these studies found that in addition to brain tumors, these studies have been associated with
the development of other cancers and diseases 。 Robert Jenkins, MD, said, "Although we have a deep understanding of the biological function of germline alterations inside genes encoding proteins, we still have little understanding of the biological functions of germline alterations outside the genes encoding proteins, which interact with other mutations in cells to accelerate tumor formation
.

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Based on the latest understanding of this mechanism of action, future research may hopefully help develop new specific therapies to target changes in the action of rs55705857, and this study provides new insights to help clinicians determine whether patients have gliomas
before surgery.
The researchers speculated that rs55705857 might accelerate the development of low-grade gliomas, but they were very surprised
by the magnitude of this acceleration.
Dr.
Schramek said there may be many, perhaps thousands, of changes beyond the genes associated with cancer development and other diseases, but only a very few mechanisms of action can be understood
.

The results suggest that using modern molecular/cell biology tools, scientists may be able to unravel most of the mechanisms of action of such alterations; In summary, this study reveals the mechanism
by which approximately 40% of patients with low-grade human gliomas may have a genetic predisposition to lethal gliomas.
(Bio Valley Bioon.
com)

Original source:

Connor Yanchus, Kristen L Drucker, Thomas M Kollmeyer，et al.
 A noncoding single-nucleotide polymorphism at 8q24 drives IDH1 -mutant glioma formation, Science (2022).
DOI: 10.
1126/science.
abj2890