Researchers at the Children’s Hospital Boston and Harvard Medical School identified a gene in zebrafish that appears to be responsible for the development of melanoma in humans.
The scientists led by Craig J. Ceol, Yariv Houvras and Leonard I. Zon and collaborators from several other institutions published details of their study using zebrafish in the journal Nature.
Zebrafish (Danio rerio) is a common tropical aquarium fish widely used as a model in scientific research. The fish is named for the five uniform horizontal dark blue stripes on each side of the body towards the tail. The pigmentation of the stripes is caused by melanocytes which occasionally, because of increased levels of the enzyme produced by the SETDB1 gene, induce the generation of melanoma tumours.
Ceol and colleagues used zebrafish to isolate the oncogene SETDB1. This gene, which in humans is located in chromosome 1, carries de code for production of histone-lysine N-methyltransferase SETDB1. This enzyme was found to accelerate melanoma formation. Scientists know that melanoma arises from affected melanocytes, the cells producing the dark pigment melanin, responsible for human skin colour.
To find the genes that were causing the melanoma tumour development, the researchers applied a technique to amplify the genes and place them in cultured melanocytes.
Thus, after analyzing more than 2,100 tumours from more than 3,000 zebrafish, they found that in animals with melanoma gene SETDB1 the tumours not only developed earlier, but also grew faster and more deeply invaded the muscle and surrounding tissues.
Subsequently, they analyzed about 100 human tumours and found that in 70% of the affected tissues, the SETDB1 enzyme was present at higher levels. According to professor Ceol, the finding could lead to a new way to diagnose and treat malignant melanoma."These results indicate that the SETDB1 may be involved in the formation of most human melanomas," says Professor Ceol.
The researchers believe that this oncogene may also be involved in other diseases such as ovarian, breast and liver cancer, but further research is needed to demonstrate it.
Malignant melanoma is not the most common form of skin cancer, but is the most serious and the cases have increased worldwide in recent decades. According to the World Health Organization, between 2 and 3 million cases of non-melanoma skin cancer are diagnosed each year. Additionally, each year malignant melanoma affects about 132,000 people causing about 65,000 deaths worldwide.