Viral status predicts patterns of genome methylation and decitabine response in Merkel cell carcinoma
Journal of Investigative Dermatology Sep 02, 2021
Harms PW, Verhaegen ME, Vo JN, et al. - The data suggest that viral status predicts Merkel cell carcinoma (MCC) genomic methylation patterns and that decitabine (DAC), a hypomethylating agent, may be therapeutically beneficial against MCC through anti-proliferative effects, cell death, and enhanced immune recognition.
The authors compared genome-wide DNA methylation in 16 MCC cell lines from both molecular subclasses to other cancer types and discovered that MCC's overall profile is comparable to that of small cell lung carcinoma.
There were 2,260 differently methylated sites when virus-positive and virus-negative MCC were compared.
DAC increased antigen-presenting apparatus expression in MCC cell lines and boosted HLA-A membrane expression in virus-positive and virus-negative MCC xenograft tumors.
In virus-positive MCC cell lines, DAC also caused significant caspase- and large T antigen-independent cell death, but virus-negative MCC cell lines showed lower proliferation without increased cell death.
DAC reduced the size of virus-positive tumors in mouse xenografts, but not virus-negative tumors.
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