Scientists from Yale University have identified new biomarkers that will help develop more effective treatment strategies to fight melanoma, the most serious form of skin cancer.
The research team has mapped chemical modifications of DNA in the melanoma genome that will open new avenues for developing improved therapies.
AdvertisementIn addition to mutations to the DNA code that can cause malignancies, epigenetic changes - alterations to the chemical modifications of DNA that regulate genes - are frequent in a number of diseases, including cancer.
If the normal epigenetic patterns that regulate gene expression are disrupted, cellular functions can go awry and lead to disease.
Lead researchers Dr Ruth Halaban and Dr Sherman Weissman of Yale University investigated genome-wide epigenetic changes, termed DNA methylation, in melanoma cells.
"This is of particular importance in melanomas, because a major etiological factor is sun exposure," Halaban said, explaining that inflammation and reactive oxygen species caused by the sun can produce epigenetic changes and mutations.
Halaban added that because DNA methylation can be reversed, it is an attractive target for cancer therapy.
The team then focused on five genes in particular, three of which had not been implicated in melanoma until now.
In clinical specimens, methylation of these promoters was predominantly detected in advanced-stage tumors, suggesting that these markers will be useful for monitoring tumor progression.
Furthermore, they found that by treating melanoma cells with a drug called decitabine, an inhibitor of DNA methylation, these genes could be reactivated.
Halaban suggests that by combining their method for finding methylation markers with the latest DNA sequencing technologies, researchers will be able to uncover genes where an interaction between genetic mutations and epigenetic changes play a role in the development of melanoma, and perhaps other cancers.
With this information, researchers can devise even more effective strategies to combat the disease.
The study is published in Genome Research.
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