EZH2 Gene Mutation Drives Lymphoma And Melanoma

Researchers at University of North Carolina at Chapel Hill have recently shown how a genetic mutation can drive the most common type of lymphoma as well as melanoma, the deadliest form of skin cancer.

Their work centered on a specific mutation of EZH2, a gene previously known to regulate cell fate. The team also tested an investigational drug to block a protein made by the gene.

Norman Sharpless M.D, director of the University of North Carolina Lineberger Comprehensive Cancer Center, explained:

“We have shown that the biology of tumors driven by this mutation is distinct from other types of lymphoma and melanoma, and that these tumors require persistent malfunction of EZH2 for growth. And with our collaborators, we have shown that a potential new drug designed to target EZH2 mutations in such cancers is very active in our laboratory models.”

This particular mutation is a relatively common event in diverse cancers, occurring in approximately 20 percent of B-cell lymphomas, 5 percent of melanomas, and at lower frequency in a variety of other cancers, Sharpless adds. The findings suggest that thousands of people in the United States annually develop cancer driven by this mutation.

The researchers determined that a mutation in the EZH2 gene alone is sufficient to drive B-cell lymphoma. In contrast, for melanoma, the EZH2 mutation occurs in combination with mutations of the BRAF gene, which occurs in about half of melanoma patients.

First author George P. Souroullas, a research scientist at UNC Lineberger and the UNC School of Medicine genetics department, says the findings could have important implications for both treatment and further drug development.

More concretely, their findings in melanoma indicate that inhibitors of the protein created by the EZH2 gene might work well in combination with inhibitors of BRAF, which are already approved by the US Food and Drug Administration as melanoma therapy.

Furthermore, their findings suggest that EZH2 inhibitors could be an effective strategy in some patients with melanoma or B-cell lymphoma, he adds.

“While there has been significant progress in recent years against cancers such as lymphoma and melanoma, many patients still fail these newer therapies and need further options for therapy,” Sharpless says.

Original Study: An oncogenic Ezh2 mutation induces tumors through global redistribution of histone 3 lysine 27 trimethylation

Image: Wellcome Photo Library, Wellcome Images