The role of aberrant DNA methylation in cancer initiation and clinical impacts

被引：11

作者：

Geissler, Franziska ^{[1
]}

Nesic, Ksenija ^{[1
,2
]}

Kondrashova, Olga ^{[3
]}

Dobrovic, Alexander ^{[4
]}

Swisher, Elizabeth M. ^{[5
]}

Scott, Clare L. ^{[1
,2
,6
,7
,8
,9
]}

J. Wakefield, Matthew ^{[6
,10
]}

机构：

[1] Walter & Eliza Hall Inst Med Res, Parkville, Vic, Australia

[2] Univ Melbourne, Dept Med Biol, Parkville, Vic, Australia

[3] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia

[4] Univ Melbourne, Dept Surg, Austin Hlth, Heidelberg, Vic, Australia

[5] Univ Washington, Seattle, WA USA

[6] Univ Melbourne, Dept Obstet & Gynaecol, Parkville, Vic, Australia

[7] Peter MacCallum Canc Ctr, Dept Surg Oncol, Melbourne, Vic, Australia

[8] Royal Womens Hosp, Parkville, Vic, Australia

[9] Royal Melbourne Hosp, Parkville, Vic, Australia

[10] Walter & Eliza Hall Inst Med Res, 1G Royal Parade, Parkville, VIC 3052, Australia

来源：

THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY | 2024年 / 16卷

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

BRCA-related cancers; diagnosis; epigenomics; genomics; genomic testing; homologous recombination deficiency; oncogenic driver mutations; targeted therapy; therapeutic resistance; TUMOR-SUPPRESSOR GENES; MISMATCH REPAIR-DEFICIENCY; MLH1 PROMOTER METHYLATION; CELL LUNG-CANCER; MICROSATELLITE INSTABILITY; COLORECTAL-CANCER; BRCA1; PROMOTER; LYNCH SYNDROME; EPIGENETIC CHANGES; SOMATIC MUTATIONS;

D O I：

10.1177/17588359231220511

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. Silencing genes role in initiation of cancer and clinical impactsGenes can be silenced by molecular tags being placed on them. This is a normal process that controls when and where genes are available to be used. In some cases this silencing can be incorrectly applied to genes involved in preventing cancer, causing cancer initiation and progression. This review discusses the role of one of these tagging processes, DNA methylation and its role in initiation of cancer and implications for treatment.

引用

页数：23

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