Genetics and epigenetics of cutaneous malignant melanoma: A concert out of tune

Karin van den Hurk, Hanneke E. C. Niessen, Jurgen Veeck, Joost J. van den Oord, Maurice A. M. van Steensel, Axel zur Hausen, Manon van Engeland, Veronique J. L. Winnepenninckx*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

50 Citations (Web of Science)

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.
Original languageEnglish
Pages (from-to)89-102
JournalBiochimica et Biophysica Acta-reviews on Cancer
Volume1826
Issue number1
DOIs
Publication statusPublished - Aug 2012

Keywords

  • Melanoma
  • Genetics
  • Epigenetics
  • DNA methylation
  • MicroRNA
  • Chromatin remodeling

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