title: Genetics and epigenetics of cutaneous malignant melanoma: a concert out of tune.
abstract: Cutaneous malignant melanoma (CMM) is the most life-threatening neoplasm of the skin and is considered a major health problem as both incidence and mortality rates continue to rise. Once CMM has metastasized it becomes therapy-resistant and is an inevitably deadly disease. Understanding the molecular mechanisms that are involved in the initiation and progression of CMM is crucial for overcoming the commonly observed drug resistance as well as developing novel targeted treatment strategies. This molecular knowledge may further lead to the identification of clinically relevant biomarkers for early CMM detection, risk stratification, or prediction of response to therapy, altogether improving the clinical management of this disease. In this review we summarize the currently identified genetic and epigenetic alterations in CMM development. Although the genetic components underlying CMM are clearly emerging, a complete picture of the epigenetic alterations on DNA (DNA methylation), RNA (non-coding RNAs), and protein level (histone modifications, Polycomb group proteins, and chromatin remodeling) and the combinatorial interactions between these events is lacking. More detailed knowledge, however, is accumulating for genetic and epigenetic interactions in the aberrant regulation of the INK4b-ARF-INK4a and microphthalmia-associated transcription factor (MITF) loci. Importantly, we point out that it is this interplay of genetics and epigenetics that effectively leads to distorted gene expression patterns in CMM.
authors.affiliation: Department of Pathology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Karin
authors.initials: K
authors.lastname: van den Hurk
authors.forename: Hanneke E C
authors.initials: HE
authors.lastname: Niessen
authors.forename: Jürgen
authors.initials: J
authors.lastname: Veeck
authors.forename: Joost J
authors.initials: JJ
authors.lastname: van den Oord
authors.forename: Maurice A M
authors.initials: MA
authors.lastname: van Steensel
authors.forename: Axel
authors.initials: A
authors.lastname: Zur Hausen
authors.forename: Manon
authors.initials: M
authors.lastname: van Engeland
authors.forename: Véronique J L
authors.initials: VJ
authors.lastname: Winnepenninckx
mesh_terms: D042002:Chromatin Assembly and Disassembly; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015870:Gene Expression; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: D035683:MicroRNAs