Until now, researchers thought of errors in DNA as the all-powerful arbiters of cancer. But a new study of a type of nerve cancer shows that DNA's message-bearer, RNA, can also lead cells astray. A last-minute edit to the RNA code that controls a tumor-suppressing protein tips the scales in favor of tumor growth.
Type 1 neurofibromatosis (NF1) is an inherited disease that afflicts about 1 in 4000 people around the world. Benign and, in rare cases, malignant tumors grow on and around nerves. The tumors cause disfigurement and pain and can disrupt functioning in nearby organs. The disease takes hold when levels of neurofibromin, a tumor-suppressing protein that helps control cell growth, fall too low. But researchers still don't know why the symptoms vary so much, even within families.
Gastroenterologist Nicholas Davidson at Washington University Medical School in St. Louis and his colleagues studied 34 malignant NF1 tumors to find an explanation. To their surprise, they found that some copies of the messenger RNA (mRNA) responsible for building neurofibromin had been altered. A single nucleotide had been changed in the mRNAs' sequences, producing a genetic "stop" sign that prevented them from building neurofibromin, they report in the January issue of the American Journal of Human Genetics.
What changed the mRNA's sequence? The researchers aren't sure, but they suspect an enzyme called apobec-1 may be to blame. This enzyme is normally found in the intestine, where it makes a minor change in another mRNA. But Davidson's team found that eight of the 34 most aggressive tumors had the highest levels of both edited neurofibromin mRNA and apobec-1, suggesting the misdirected enzyme might be responsible for the faulty mRNA.
It's highly likely that mRNA editing plays a role in the tumor development of other cancers as well, says cancer researcher Tyler Jacks of the MIT Center for Cancer Research. He's betting that "we're going to see more of this" in the future.
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