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DNA methylation in circulating tumour DNA as a biomarker for cancer.

ABSTRACT: Free circulating DNA, which is thought to be derived from the primary tumour, can be detected in the blood of patients with cancer. Detection of genetic and epigenetic alteration in this tumour DNA offers a potential source of development of prognostic and predictive biomarkers for cancer. One such change is DNA methylation of the promotor region of tumour suppressor genes. This causes down regulation of tumour suppressor gene expression, a frequent event in carcinogenesis. Hypermethylation of the promotor region of a number of genes has been detected in many tumour types and more recently these changes have been detected in circulating tumour DNA. This review will summarise the literature detailing DNA methylation in circulating tumour DNA and discuss some of the current controversies and technical challenges facing its use as a potential biomarker for cancer.

SUBMITTER: Board RE

PROVIDER: S-EPMC2717819 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

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DNA methylation in circulating tumour DNA as a biomarker for cancer.

Board Ruth E RE Knight Lucy L Greystoke Alastair A Blackhall Fiona H FH Hughes Andrew A Dive Caroline C Ranson Malcolm M

Biomarker insights 20080125

Free circulating DNA, which is thought to be derived from the primary tumour, can be detected in the blood of patients with cancer. Detection of genetic and epigenetic alteration in this tumour DNA offers a potential source of development of prognostic and predictive biomarkers for cancer. One such change is DNA methylation of the promotor region of tumour suppressor genes. This causes down regulation of tumour suppressor gene expression, a frequent event in carcinogenesis. Hypermethylation of t ...[more]

PMID: 19662228

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Project description:BackgroundEarly detection and prognosis prediction of colorectal cancer (CRC) can significantly reduce CRC-related mortality. Recently, circulating tumour DNA (ctDNA) methylation has shown good application foreground in the early detection and prognosis prediction of multiple tumours.MethodsThis multicentre cohort study evaluated ctDNA methylation haplotype patterns based on archived plasma samples (collected between 2010 and 2018) from 1138 individuals at two medical centres: Fudan University Shanghai Cancer Center (Shanghai, China) and Southern Medical University Nanfang Hospital (Guangzhou, Guangdong, China), including 366 healthy individuals, 182 patients with advanced adenoma (AA), and 590 patients with CRC. Samples were processed using the ColonES assay, a targeted bisulfite sequencing method that detects ctDNA methylation haplotype patterns in 191 genomic regions. Among these 1138 samples, 748 were used to develop a classification model, and 390 served as a blinded cohort for independent validation. The study is registered at https://register.clinicaltrials.gov with the unique identifier NCT03737591.ResultsThe model obtained from unblinded samples discriminated patients with CRC or AA from normal controls with high accuracy. In the blinded validation set, the ColonES assay achieved sensitivity values of 79.0% (95% confidence interval (CI), 66%-88%) in AA patients and 86.6% (95% CI, 81%-91%) in CRC patients with a specificity of 88.1% (95% CI, 81%-93%) in healthy individuals. The model area under the curve (AUC) for the blinded validation set was 0.903 for AA samples and 0.937 for CRC samples. Additionally, the prognosis of patients with high preoperative ctDNA methylation levels was worse than that of patients with low ctDNA methylation levels (p = 0.001 for relapse-free survival and p = 0.004 for overall survival).InterpretationWe successfully developed and validated an accurate, noninvasive detection method based on ctDNA methylation haplotype patterns that may enable early detection and prognosis prediction for CRC.FundingThe Grant of National Natural Science Foundation of China (No.81871958), National Natural Science Foundation of China (No. 82203215), Shanghai Science and Technology Committee (No. 19140902100), Scientific Research Fund of Fudan University (No.IDF159052), Shanghai Municipal Health Commission (SHWJRS 2021-99), and Shanghai Sailing Program (22YF1408800).

Dataset Information

DNA methylation in circulating tumour DNA as a biomarker for cancer.

Publications

DNA methylation in circulating tumour DNA as a biomarker for cancer.

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