title: The DNA methylation landscape of human melanoma.
abstract: Using MIRA-seq, we have characterized the DNA methylome of metastatic melanoma and normal melanocytes. Individual tumors contained several thousand hypermethylated regions. We discovered 179 tumor-specific methylation peaks present in all (27/27) melanomas that may be effective disease biomarkers, and 3113 methylation peaks were seen in >40% of the tumors. We found that 150 of the approximately 1200 tumor-associated methylation peaks near transcription start sites (TSSs) were marked by H3K27me3 in melanocytes. DNA methylation in melanoma was specific for distinct H3K27me3 peaks rather than for broadly covered regions. However, numerous H3K27me3 peak-associated TSS regions remained devoid of DNA methylation in tumors. There was no relationship between BRAF mutations and the number of methylation peaks. Gene expression analysis showed upregulated immune response genes in melanomas presumably as a result of lymphocyte infiltration. Down-regulated genes were enriched for melanocyte differentiation factors; e.g., KIT, PAX3 and SOX10 became methylated and downregulated in melanoma.
authors.affiliation: Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503, USA; Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
authors.forename: Seung-Gi
authors.initials: SG
authors.lastname: Jin
authors.affiliation: Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
authors.forename: Wenying
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
authors.forename: Xiwei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503, USA; Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA. Electronic address: gerd.pfeifer@vai.org.
authors.forename: Gerd P
authors.initials: GP
authors.lastname: Pfeifer
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D019175:DNA Methylation; D020869:Gene Expression Profiling / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007109:Immunity / Q000235:genetics; D008239:Lysine / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism; D008745:Methylation; D024363:Transcription Initiation Site
chemical_list: D006657:Histones; D008239:Lysine
keywords: BRAF; DNA methylation; H3K27me3; Melanocytes; Melanoma; Polycomb