At a glance:
- By NANCY FLIESLER | Boston Children's
- Researchers have identified gene mutations that cause cancer in a previously unknown way.
- Affected cells lose the ability to get rid of defective strands of RNA.
- The findings apply to many different cancers and could lead to development of better treatments for them.
Cancer can stem from mutations in many different genes.
New research pinpoints a gene that, when mutated, causes cancer through a mechanism scientists haven't seen before: cells do lose the ability to dispose of their trash, namely defective strands of RNA.
This mechanism appears to cut across many different malignancies and could present a whole new set of molecules for cancer drugs to target, as reported April 21 in Science by a team from Harvard Medical School, Boston Children's Hospital, and Dana-Farber Cancer Institute.
While studying zebrafish, Megan Insco, HMS instructor in medicine who was a research fellow in the lab of Leonard Zon at HMS and Boston Children's at the time, identified a tumor-suppressing gene called CDK13. When mutated, it expedited the development of melanoma.
The same gene was also mutated in many human melanomas, she found.
But what was really surprising was how the CDK13 mutation causes cancer.
Investigating the RNAs made by melanoma cells, Insco saw multiple short, defective RNAs. She immediately shared this odd finding with Zon.
"I said, 'that definitely is interesting,'" recalled Zon, professor of stem cell and regenerative biology at Harvard University and director of the Stem Cell Research Program at Boston Children's. "It took years to figure out what it meant."
A broken vacuum cleaner
It's normal for cells to make a small number of short, defective RNAs. Typically, surveillance machinery in the cell nucleus spots these and disposes of them.
"There are hundreds of steps in making RNAs, and sometimes it doesn't go right," explained Insco, who now runs her own lab at Dana-Farber.
"They're mistakes that are usually discarded. In this case, we found that the cell was not cleaning them up. The vacuum cleaner was broken, so the RNAs were building up."
These "junk" RNA molecules by themselves dramatically accelerated the progression of melanoma. (In her lab, Insco will investigate whether the effect is due to the RNAs themselves or abnormal proteins made from the RNAs.
