KMT2C and KMT2D aberrations in breast cancer

Emily Tinsley; Philip Bredin; Sinead Toomey; Bryan T Hennessy; Simon J Furney

doi:10.1016/j.trecan.2024.02.003

KMT2C and KMT2D aberrations in breast cancer

Trends Cancer. 2024 Mar 6:S2405-8033(24)00029-3. doi: 10.1016/j.trecan.2024.02.003. Online ahead of print.

Authors

Emily Tinsley¹, Philip Bredin², Sinead Toomey², Bryan T Hennessy³, Simon J Furney⁴

Affiliations

¹ Genomic Oncology Research Group, Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
² Medical Oncology Group, Department of Molecular Medicine, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
³ Medical Oncology Group, Department of Molecular Medicine, RCSI University of Medicine and Health Sciences, Dublin, Ireland; Department of Medical Oncology, Beaumont Hospital, Dublin, Ireland. Electronic address: bryanhennessy74@gmail.com.
⁴ Genomic Oncology Research Group, Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland. Electronic address: simonfurney@rcsi.ie.

PMID: 38453563
DOI: 10.1016/j.trecan.2024.02.003

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