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.