The Cancer COMPASS: Navigating the Functions of MLL Complexes in Cancer

Cancer Genet. 2015 May;208(5):178-91. doi: 10.1016/j.cancergen.2015.01.005. Epub 2015 Jan 30.

Abstract

The mixed-lineage leukemia family of histone methyltransferases (MLL1-4, or KMT2A-D) were previously linked to cancer through the founding member, MLL1/KMT2A, which is often involved in translocation-associated gene fusion events in childhood leukemias. However, in recent years, a multitude of tumor exome sequencing studies have revealed that orthologues MLL3/KMT2C and MLL2/KMT2D are mutated in a significant percentage of a large variety of malignancies, particularly solid tumors. These unexpected findings necessitate a deeper inspection into the activities and functional differences between the MLL/KMT2 family members. This review provides an overview of this protein family and its relation to cancers, focusing on the recent links between MLL3/KMT2C and MLL2/4/KMT2D and their potential roles as tumor suppressors in an assortment of cell types.

Keywords: COMPASS complex; Epigenetics; chromatin; enhancers; lysine methyltransferase.

Publication types

  • Review
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Carcinoma / genetics*
  • Cell Transformation, Neoplastic / genetics*
  • Chromatin / genetics
  • DNA-Binding Proteins / genetics*
  • Epigenesis, Genetic
  • Histone-Lysine N-Methyltransferase / genetics
  • Humans
  • Leukemia / genetics*
  • Myeloid-Lymphoid Leukemia Protein / genetics
  • Neoplasm Proteins / genetics*

Substances

  • Chromatin
  • DNA-Binding Proteins
  • KMT2A protein, human
  • KMT2C protein, human
  • KMT2D protein, human
  • Neoplasm Proteins
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase
  • MLL4 protein, human