Researchers from Boston Children’s Hospital have visually followed the emergence and spread of cancer form its first cell to other parts of an animal. The pioneering study, published in the journal Science, will help scientists understand cancer development and find new treatments.
Some cells that present typical cancer mutations do not behave like cancer cells. Dr. Zon and colleagues were able to track the sequence of mutations and cell behavior. They discovered that, apart from the mutations recognized as cancer-related, an oncogene activation of tumor suppressor deactivation must happen. From this point, the researchers identified a series of changes that end up in the cell reverting to a stem cell state. New treatments could be based on targeting those genetic changes, preventing cancer from starting.
Specifically, the researchers followed the activation of the crestin gene in zebrafish that had both a mutation in the gene BRAFV600E -found in bening human moles- and in the tumor suppressor p53. Crestin activation, which happens during embryonic development, could be visually tracked by linking it to green fluorescent protein (GFP). Normally, crestin is turned off after a certain developmental stage and is never active again. However, the researchers observed certain unexpected green spots in some cells, meaning that crestin was back on. 100% of those cells became cancerous.
The genes activated in these early cancer cells where exactly the same that were active in the stem cells that become melanocytes, the pigment cells of the neural crest. The same genes are activated in human melanoma. The gene activation pattern is a reversion to neural crest status.
To find the cells that became cancerous, Dr. Charles Kaufman observed the zebrafish swimming around under a fluorescent filter. In all cases, when he identified a green cluster of cells, these became a tumor. In two cases he could follow the cancer development from its first cell.
This study could inspire new genetic tests on suspicious moles, checking the activation of neural crest development genes. The authors are now investigating the DNA regulatory sequences (enhancers) that activate that genetic program
Source: Boston Children’s Hospital