Harms PW, Verhaegen ME, Vo JN, et al. - Classification of Merkel cell carcinoma (MCC), an aggressive cutaneous neuroendocrine carcinoma, is done as Merkel cell polyomavirus-positive (virus positive [VP]) or Merkel cell polyomavirus-negative (virus negative [VN]). In this study, viral status has been identified as predictive of genomic methylation patterns in MCC and decitabine is suggested as therapeutically effective against MCC through antiproliferative effects, cell death, and increased immune recognition.

• Genome-wide DNA methylation in 16 MCC cell lines from both molecular subclasses was described in comparison with other cancer types.

• The overall profile of MCC is identified as similar to that of small-cell lung carcinoma.

• A total of 2,260 differentially methylated positions were identified when VP MCC was compared with VN MCC.

• The hypomethylating agent decitabine led to upregulation of the expression of antigen-presenting machinery in MCC cell lines and stimulation of the membrane expression of HLA-A in VP and VN MCC xenograft tumors.

• In addition, decitabine induced prominent caspase- and large T antigen‒independent cell death in VP MCC, whereas reduced proliferation appeared in VN MCC cell lines without increased cell death.

• In mouse xenografts, the size of VP tumors but not that of VN tumors reduced significantly after treatment with decitabine.