KMT2C and KMT2D aberrations in breast cancer

Trends Cancer. 2024 Jun;10(6):519-530. doi: 10.1016/j.trecan.2024.02.003. Epub 2024 Mar 7.

Abstract

KMT2C and KMT2D are histone lysine methyltransferases responsible for the monomethylation of histone 3 lysine 4 (H3K4) residues at gene enhancer sites. KMT2C/D are the most frequently mutated histone methyltransferases (HMTs) in breast cancer, occurring at frequencies of 10-20% collectively. Frequent damaging and truncating somatic mutations indicate a tumour-suppressive role of KMT2C/D in breast oncogenesis. Recent studies using cell lines and mouse models to replicate KMT2C/D loss show that these genes contribute to oestrogen receptor (ER)-driven transcription in ER+ breast cancers through the priming of gene enhancer regions. This review provides an overview of the functions of KMT2C/D and outlines the recent clinical and experimental evidence of the roles of KMT2C and KMT2D in breast cancer development.

Keywords: KMT2C; KMT2D; breast cancer; chromatin remodelling; enhancers; histone lysine methyltransferases.

Publication types

  • Review

MeSH terms

  • Animals
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • DNA-Binding Proteins* / genetics
  • DNA-Binding Proteins* / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism
  • Humans
  • Mice
  • Mutation
  • Neoplasm Proteins* / genetics
  • Neoplasm Proteins* / metabolism
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism

Substances

  • KMT2D protein, human
  • KMT2C protein, human
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • Histone-Lysine N-Methyltransferase
  • Receptors, Estrogen