The MYC Enhancer-ome: Long-Range Transcriptional Regulation of MYC in Cancer

Trends Cancer. 2018 Dec;4(12):810-822. doi: 10.1016/j.trecan.2018.10.003. Epub 2018 Nov 2.

Abstract

MYC is one of the most important oncogenes in cancer. Indeed, MYC is upregulated in 50-60% of all tumors. MYC overexpression can be achieved through a variety of mechanisms, including gene duplications, chromosomal translocations, or somatic mutations leading to increased MYC stability. However, recent studies have identified numerous tissue-specific noncoding enhancers of MYC that play major roles in cancer, highlighting long-range transcriptional regulation of MYC as a critical novel mechanism leading to MYC hyperactivation and as a potential target for new therapeutic strategies in the near future. Here we summarize the regions and mechanisms involved in the long-range transcriptional regulation of MYC, underscoring the relevance of MYC enhancers both in normal physiological development and in MYC-driven cancer initiation and progression.

Keywords: MYC; SNP; cancer; enhancer; long-range transcriptional regulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Enhancer Elements, Genetic / genetics*
  • Gene Duplication
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mutation
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism
  • Up-Regulation

Substances

  • MYC protein, human
  • Proto-Oncogene Proteins c-myc