Epigenetic Angle on Melanoma: High Levels of H2A.Z.2 Histone Variant Promote Melanoma Growth; Blocking H2A.Z.2 Function Halts Tumor Growth and Kills Melanoma Cells

Melanoma patients with high levels of a histone variant protein that controls the expression of pro-growth genes are less likely to survive, according to a study led by researchers at the Icahn School of Medicine at Mount Sinai and published online on June 4, 2015 in the journal Molecular Cell. The article is titled “Histone Variant H2A.Z.2 Mediates Proliferation and Drug Sensitivity of Malignant Melanoma.” “The research team found that the protein, a histone variant called H2A.Z.2, promotes the abnormal growth seen in melanoma cells as they develop into difficult-to-treat tumors. H2A.Z.2 is part of the chromosome structure (histones) that packages genes, and has the ability to switch them on and off. Having high levels of this protein aberrantly activates growth-promoting genes in melanoma cells. An emerging theory in cancer research is that abnormal growth may result, not only from unfortunate mutations in patients' genes, but also from epigenetic mechanisms that turn genes on and off. In the current study, the authors found that blocking the functions of H2A.Z.2, either alone or in combination with cancer therapies, effectively blocked tumor growth and killed melanoma cells. "Cancer is a disease consisting of both genetic and epigenetic changes," said Emily Bernstein, Ph.D., Associate Professor of Oncological Sciences and Dermatology, at the Icahn School of Medicine at Mount Sinai, and lead author of the current study. "I believe that the study of epigenetic mechanisms may lead to the development of new approaches for molecular diagnosis and targeted treatments. Here we show that the histone variant H2A.Z.2 drives melanoma progression by affecting chromatin structure," said Dr. Bernstein. "This is the first study to identify a specific role for the histone variant H2A.Z.2 in any tumor type.
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