The findings of the team of researchers, published in Science last week, has helped identify exactly at what point in the cycle of development that a cancer-prone cell makes the conversion to one that is malignant.
Charles Kaufman, MD, PhD, a postdoctoral fellow in the Zon Laboratory at Boston Children’s Hospital and the paper’s first author, describes this critical point as one that “…occurs after activation of an oncogene or loss of a tumor suppressor, and involves a change that takes a single cell back to a stem cell state.”
To track this development, the research team used a zebrafish model with a human cancer mutation called BRAFV600E – commonly found in non-cancerous moles – that was also lacking the p53, a well-known tumor suppressor gene. A gene called crestin was of particular interest to the scientists due to its association with stem cells. Normally, after embryonic development, crestin and related genes are programmed to shut off. However, for unknown reasons certain cells prompt crestin and related genes to switch back on. The zebrafish genes were fluorescently tagged and would light up if crestin was turned on. In 100 percent of cases, once one green spot was identified on a zebrafish it consistently developed into melanoma.
The researchers believe that these findings have the potential to lead to a “new genetic test for suspicious moles” and they are also digging deeper to identify new therapeutic targets, such as regulatory DNA elements called super-enhancers, to prevent moles from becoming cancerous. Additionally, these findings can potentially span beyond melanoma to many other cancer types which can lead to more exciting advancements throughout the field of cancer research.