Disabled Editing in Tumors

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Science  14 Dec 2001:
Vol. 294, Issue 5550, pp. 2253
DOI: 10.1126/science.294.5550.2253a

As tumor cells progress to a more malignant state, they accumulate a number of genetic alterations, including some that can disrupt the fundamental mechanisms regulating gene expression. One of the posttranscriptional regulatory mechanisms that might be vulnerable in tumor cells is RNA editing, an enzyme-mediated process in which newly synthesized messenger RNAs (mRNAs) undergo selective base modifications that can dramatically alter the function of the encoded protein.

Studying RNA editing patterns in human glioblastoma multiforme (GBM), a highly malignant form of brain tumor, Maas et al. discovered that the mRNA encoding the glutamate receptor subunit B was severely underedited at a nucleotide position that must be changed from adenosine to inosine for normal receptor function. Intriguingly, underediting at this position has been linked previously to epileptic seizures, a complication that often is seen in patients with GBM. Consistent with the loss of A → I RNA editing, the tumors showed reduced activity of adenosine deaminase 2 (ADAR2), the enzyme responsible for this modification.

Other tumor-associated alterations in RNA editing are described in a separate study by Mukhopadhyay et al., who found evidence of aberrant C → U editing of neurofibromin mRNA in about 25% of peripheral nerve-sheath tumors from patients with neurofibromatosis type I. The same subset of tumors also showed enhanced expression of the RNA editing enzyme catalyzing this modification, apobec-1. The functional role that deregulated RNA editing plays in tumorigenesis is an important issue that remains to be explored.—PAK

Proc. Natl. Acad. Sci. U.S.A., 98, 14687 (2001); Am. J. Hum. Genet., in press.

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