NEW YORK (Reuters Health) - Activating mutations in the gene for the serine/threonine kinase BRAF play a critical role in nevus formation and the development of melanoma, according to findings from the first-ever animal study to examine this association. However, such mutations alone may not be sufficient for malignancy to occur.
The findings are based on a study in which researchers used zebrafish to assess the effect of BRAF mutations on nevi and melanoma. “The visual nature of the fish makes in an attractive model for studying cancer,” senior author Dr. Leonard Zon, from Harvard Medical School in Boston, said in a statement. “We can track a cancer and follow the fate of individual cells as the tumor grows and spreads.”
In the study, the researchers created fish that expressed the most common human BRAF mutant, known as V600E. The scales of these animals were then compared with that of fish expressing wild-type BRAF.
The researchers’ findings appear in the February 8th issue of Current Biology.
Expression of mutant BRAF in otherwise normal fish led to patches of ectopic melanocytes, but no melanomas were seen. By contrast, such mutations readily produced melanomas in fish already lacking the tumor suppressor gene p53. These melanomas were histologically very similar to their human counterparts.
“Taken together, this work establishes a melanoma model in zebrafish, provides the first zebrafish example of a genetic interaction promoting cancer, and demonstrates the pathological relevance of the BRAF V600E mutation in an animal system,” the authors state.
Source: Current Biol 2005;15:249-254. [ Google search on this article ]
MeSH Headings:Cyprinidae: Cypriniformes: ZebrafishCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
