Genome-scale detection of hypermethylated CpG islands in circulating cell-free DNA of hepatocellular carcinoma patients
Despite advances in DNA methylome analyses of cells and tissues, current techniques for genome-scale profiling of DNA methylation in circulating cell-free DNA (ccfDNA) remain limited. Here we describe a methylated CpG tandems amplification and sequencing (MCTA-Seq) method that can detect thousands o...
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| Language: | English |
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Nature Publishing Group
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650428/ |
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pubmed-46504282015-12-01 Genome-scale detection of hypermethylated CpG islands in circulating cell-free DNA of hepatocellular carcinoma patients Wen, Lu Li, Jingyi Guo, Huahu Liu, Xiaomeng Zheng, Shengmin Zhang, Dafang Zhu, Weihua Qu, Jianhui Guo, Limin Du, Dexiao Jin, Xiao Zhang, Yuhao Gao, Yun Shen, Jie Ge, Hao Tang, Fuchou Huang, Yanyi Peng, Jirun Original Article Despite advances in DNA methylome analyses of cells and tissues, current techniques for genome-scale profiling of DNA methylation in circulating cell-free DNA (ccfDNA) remain limited. Here we describe a methylated CpG tandems amplification and sequencing (MCTA-Seq) method that can detect thousands of hypermethylated CpG islands simultaneously in ccfDNA. This highly sensitive technique can work with genomic DNA as little as 7.5 pg, which is equivalent to 2.5 copies of the haploid genome. We have analyzed a cohort of tissue and plasma samples (n = 151) of hepatocellular carcinoma (HCC) patients and control subjects, identifying dozens of high-performance markers in blood for detecting small HCC (≤ 3 cm). Among these markers, 4 (RGS10, ST8SIA6, RUNX2 and VIM) are mostly specific for cancer detection, while the other 15, classified as a novel set, are already hypermethylated in the normal liver tissues. Two corresponding classifiers have been established, combination of which achieves a sensitivity of 94% with a specificity of 89% for the plasma samples from HCC patients (n = 36) and control subjects including cirrhosis patients (n = 17) and normal individuals (n = 38). Notably, all 15 alpha-fetoprotein-negative HCC patients were successfully identified. Comparison between matched plasma and tissue samples indicates that both the cancer and noncancerous tissues contribute to elevation of the methylation markers in plasma. MCTA-Seq will facilitate the development of ccfDNA methylation biomarkers and contribute to the improvement of cancer detection in a clinical setting. Nature Publishing Group 2015-11 2015-10-30 /pmc/articles/PMC4650428/ /pubmed/26516143 http://dx.doi.org/10.1038/cr.2015.126 Text en Copyright © 2015 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences http://creativecommons.org/licenses/by-nc-sa/4.0/ This license allows readers to copy, distribute and transmit the Contributionas long as it attributed back to the author. Readers are permitted to alter, transform or build upon the Contribution as long as the resulting work is then distributed under this is a similar license. Readers are notpermitted touse theContributionfor commercial purposes. Please read the full license for further details at - http://creativecommons.org/licenses/by-nc-sa/4.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Wen, Lu Li, Jingyi Guo, Huahu Liu, Xiaomeng Zheng, Shengmin Zhang, Dafang Zhu, Weihua Qu, Jianhui Guo, Limin Du, Dexiao Jin, Xiao Zhang, Yuhao Gao, Yun Shen, Jie Ge, Hao Tang, Fuchou Huang, Yanyi Peng, Jirun |
| spellingShingle |
Wen, Lu Li, Jingyi Guo, Huahu Liu, Xiaomeng Zheng, Shengmin Zhang, Dafang Zhu, Weihua Qu, Jianhui Guo, Limin Du, Dexiao Jin, Xiao Zhang, Yuhao Gao, Yun Shen, Jie Ge, Hao Tang, Fuchou Huang, Yanyi Peng, Jirun Genome-scale detection of hypermethylated CpG islands in circulating cell-free DNA of hepatocellular carcinoma patients |
| author_facet |
Wen, Lu Li, Jingyi Guo, Huahu Liu, Xiaomeng Zheng, Shengmin Zhang, Dafang Zhu, Weihua Qu, Jianhui Guo, Limin Du, Dexiao Jin, Xiao Zhang, Yuhao Gao, Yun Shen, Jie Ge, Hao Tang, Fuchou Huang, Yanyi Peng, Jirun |
| author_sort |
Wen, Lu |
| title |
Genome-scale detection of hypermethylated CpG islands in circulating cell-free DNA of hepatocellular carcinoma patients |
| title_short |
Genome-scale detection of hypermethylated CpG islands in circulating cell-free DNA of hepatocellular carcinoma patients |
| title_full |
Genome-scale detection of hypermethylated CpG islands in circulating cell-free DNA of hepatocellular carcinoma patients |
| title_fullStr |
Genome-scale detection of hypermethylated CpG islands in circulating cell-free DNA of hepatocellular carcinoma patients |
| title_full_unstemmed |
Genome-scale detection of hypermethylated CpG islands in circulating cell-free DNA of hepatocellular carcinoma patients |
| title_sort |
genome-scale detection of hypermethylated cpg islands in circulating cell-free dna of hepatocellular carcinoma patients |
| description |
Despite advances in DNA methylome analyses of cells and tissues, current techniques for genome-scale profiling of DNA methylation in circulating cell-free DNA (ccfDNA) remain limited. Here we describe a methylated CpG tandems amplification and sequencing (MCTA-Seq) method that can detect thousands of hypermethylated CpG islands simultaneously in ccfDNA. This highly sensitive technique can work with genomic DNA as little as 7.5 pg, which is equivalent to 2.5 copies of the haploid genome. We have analyzed a cohort of tissue and plasma samples (n = 151) of hepatocellular carcinoma (HCC) patients and control subjects, identifying dozens of high-performance markers in blood for detecting small HCC (≤ 3 cm). Among these markers, 4 (RGS10, ST8SIA6, RUNX2 and VIM) are mostly specific for cancer detection, while the other 15, classified as a novel set, are already hypermethylated in the normal liver tissues. Two corresponding classifiers have been established, combination of which achieves a sensitivity of 94% with a specificity of 89% for the plasma samples from HCC patients (n = 36) and control subjects including cirrhosis patients (n = 17) and normal individuals (n = 38). Notably, all 15 alpha-fetoprotein-negative HCC patients were successfully identified. Comparison between matched plasma and tissue samples indicates that both the cancer and noncancerous tissues contribute to elevation of the methylation markers in plasma. MCTA-Seq will facilitate the development of ccfDNA methylation biomarkers and contribute to the improvement of cancer detection in a clinical setting. |
| publisher |
Nature Publishing Group |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650428/ |
| _version_ |
1613503060549566464 |