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COMPASS Ascending: Emerging clues regarding the roles of MLL3/KMT2C and MLL2/KMT2D proteins in cancer

Richard J Fagan1, Andrew K Dingwall2

  • 1Stritch School of Medicine, Loyola University Chicago, Maywood, IL, 60521, USA.

Cancer Letters
|May 26, 2019
PubMed

Insights

Mutations in KMT2 genes, crucial for development, are linked to various cancers. Recent studies highlight KMT2C and KMT2D gene mutations in cancer, offering new insights into epigenetic regulation and carcinogenesis.

Area of Science:

  • Molecular Biology
  • Cancer Genomics
  • Epigenetics

Background:

  • The KMT2 (lysine methyltransferase) family regulates developmental pathways.
  • Mutations in KMT2 genes are linked to blood and solid tumor cancers.
  • KMT2A-D proteins are histone methyltransferases in COMPASS-like complexes vital for transcription.

Purpose of the Study:

  • To investigate the role of KMT2C and KMT2D gene mutations in cancer.
  • To understand the contribution of KMT2C/D proteins in epigenetic gene regulation.
  • To explore the links between KMT2C/D dysfunction and carcinogenesis.

Main Methods:

  • Analysis of large-scale tumor DNA sequencing studies.
  • Examination of cancer genomics databases.
  • Review of recent studies on KMT2C and KMT2D protein functions.

Main Results:

  • Heterozygous somatic mutations in KMT2C and KMT2D are frequently associated with human cancers.
  • Disrupted KMT2C and KMT2D proteins show potential roles in cell growth abnormalities.
  • KMT2 gene mutations, initially linked to MLL, are now recognized across multiple KMT2 family members.

Conclusions:

  • KMT2C and KMT2D mutations are significant in cancer development.
  • These findings enhance understanding of KMT2 proteins in epigenetic regulation and cancer.
  • Further research into KMT2C/D is crucial for cancer therapeutics.
Keywords:
ChromatinCo-occurrenceEpigeneticLysine methyltransferase

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