title: DNA methylation subgroups in melanoma are associated with proliferative and immunological processes.
abstract: BACKGROUND
  DNA methylation at CpG dinucleotides is modified in tumorigenesis with potential impact on transcriptional activity.
  
  
  METHODS
  We used the Illumina 450 K platform to evaluate DNA methylation patterns of 50 metastatic melanoma tumors, with matched gene expression data.
  
  
  RESULTS
  We identified three different methylation groups and validated the groups in independent data from The Cancer Genome Atlas. One group displayed hypermethylation of a developmental promoter set, genome-wide demethylation, increased proliferation and activity of the SWI/SNF complex. A second group had a methylation pattern resembling stromal and leukocyte cells, over-expressed an immune signature and had improved survival rates in metastatic tumors (p < 0.05). A third group had intermediate methylation levels and expressed both proliferative and immune signatures. The methylation groups corresponded to some degree with previously identified gene expression phenotypes.
  
  
  CONCLUSIONS
  Melanoma consists of divergent methylation groups that are distinguished by promoter methylation, proliferation and content of immunological cells.
authors.affiliation: Department of Oncology and Pathology, Clinical Sciences, Lund University Hospital, Lund University, Lund, 221 85, Sweden. martin.lauss@med.lu.se.
authors.forename: Martin
authors.initials: M
authors.lastname: Lauss
authors.affiliation: Department of Oncology and Pathology, Clinical Sciences, Lund University Hospital, Lund University, Lund, 221 85, Sweden. markus.ringner@med.lu.se.
authors.forename: Markus
authors.initials: M
authors.lastname: Ringnér
authors.affiliation: Department of Oncology and Pathology, Clinical Sciences, Lund University Hospital, Lund University, Lund, 221 85, Sweden. anna_f.karlsson@med.lu.se.
authors.forename: Anna
authors.initials: A
authors.lastname: Karlsson
authors.affiliation: Department of Oncology and Pathology, Clinical Sciences, Lund University Hospital, Lund University, Lund, 221 85, Sweden. katja.harbst@med.lu.se.
authors.forename: Katja
authors.initials: K
authors.lastname: Harbst
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway. busch.christian@gmail.com.|Department of Clinical Oncology, Haukeland University Hospital, Bergen, Norway. busch.christian@gmail.com.
authors.forename: Christian
authors.initials: C
authors.lastname: Busch
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway. juergen.geisler@medisin.uio.no.|Department of Clinical Oncology, Haukeland University Hospital, Bergen, Norway. juergen.geisler@medisin.uio.no.|Present Address: Department of Clinical Molecular Biology and Laboratory Sciences, Akershus University Hospital, Lørenskog, Norway. juergen.geisler@medisin.uio.no.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Geisler
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway. per.eystein.lonning@helse-bergen.no.|Department of Clinical Oncology, Haukeland University Hospital, Bergen, Norway. per.eystein.lonning@helse-bergen.no.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway. per.eystein.lonning@helse-bergen.no.
authors.forename: Per Eystein
authors.initials: PE
authors.lastname: Lønning
authors.affiliation: Department of Oncology and Pathology, Clinical Sciences, Lund University Hospital, Lund University, Lund, 221 85, Sweden. johan.staaf@med.lu.se.
authors.forename: Johan
authors.initials: J
authors.lastname: Staaf
authors.affiliation: Department of Oncology and Pathology, Clinical Sciences, Lund University Hospital, Lund University, Lund, 221 85, Sweden. goran_b.jonsson@med.lu.se.
authors.forename: Göran
authors.initials: G
authors.lastname: Jönsson
mesh_terms: D049109:Cell Proliferation; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic / Q000235:genetics