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Title: The role of aberrant DNA methylation in cancer initiation and clinical impacts.
Austin Authors: Geissler, Franziska;Nesic, Ksenija;Kondrashova, Olga;Dobrovic, Alexander ;Swisher, Elizabeth M;Scott, Clare L;J Wakefield, Matthew
Affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Surgery (University of Melbourne)
University of Washington, Seattle, WA, USA.
Issue Date: 2024
Date: 2024
Publication information: Therapeutic Advances in Medical Oncology 2024; 16
Abstract: Epigenetic alterations, including aberrant DNA methylation, are now recognized as bone fide hallmarks of cancer, which can contribute to cancer initiation, progression, therapy responses and therapy resistance. Methylation of gene promoters can have a range of impacts on cancer risk, clinical stratification and therapeutic outcomes. We provide several important examples of genes, which can be silenced or activated by promoter methylation and highlight their clinical implications. These include the mismatch DNA repair genes MLH1 and MSH2, homologous recombination DNA repair genes BRCA1 and RAD51C, the TERT oncogene and genes within the P15/P16/RB1/E2F tumour suppressor axis. We also discuss how these methylation changes might occur in the first place - whether in the context of the CpG island methylator phenotype or constitutional DNA methylation. The choice of assay used to measure methylation can have a significant impact on interpretation of methylation states, and some examples where this can influence clinical decision-making are presented. Aberrant DNA methylation patterns in circulating tumour DNA (ctDNA) are also showing great promise in the context of non-invasive cancer detection and monitoring using liquid biopsies; however, caution must be taken in interpreting these results in cases where constitutional methylation may be present. Thus, this review aims to provide researchers and clinicians with a comprehensive summary of this broad, but important subject, illustrating the potentials and pitfalls of assessing aberrant DNA methylation in cancer.
DOI: 10.1177/17588359231220511
ORCID: 0000-0003-3568-2008
Journal: Therapeutic Advances in Medical Oncology
Start page: 17588359231220511
PubMed URL: 38293277
Type: Journal Article
Subjects: BRCA-related cancers
genomic testing
homologous recombination deficiency
oncogenic driver mutations
targeted therapy
therapeutic resistance
Appears in Collections:Journal articles

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