Targeted deep DNA methylation analysis of circulating cell-free DNA in plasma using massively parallel semiconductor sequencing

Epigenomics. 2015;7(3):353-62. doi: 10.2217/epi.14.94.

Abstract

Aim: To set up a targeted methylation analysis using semiconductor sequencing and evaluate the potential for studying methylation in circulating cell-free DNA (cfDNA).

Materials & methods: Methylation of VIM, FBLN1, LTBP2, HINT2, h19 and IGF2 was analyzed in plasma cfDNA and white blood cell DNA obtained from eight hepatocellular carcinoma patients and eight controls using Ion Torrent™ PGM sequencer.

Results: h19 and IGF2 showed consistent methylation levels and methylation was detected for VIM and FBLN1, whereas LTBP2 and HINT2 did not show methylation for target regions. VIM gene promoter methylation was higher in HCC cfDNA than in cfDNA of controls or white blood cell DNA.

Conclusion: Semiconductor sequencing is a suitable method for analyzing methylation profiles in cfDNA. Furthermore, differences in cfDNA methylation can be detected between controls and hepatocellular carcinoma cases, even though due to the small sample set these results need further validation.

Keywords: cfDNA; early cancer detection; hepatocellular carcinoma; methylation; next-generation sequencing.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / genetics
  • DNA / blood
  • DNA Methylation*
  • Genomic Imprinting
  • High-Throughput Nucleotide Sequencing / instrumentation
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Liver Neoplasms / genetics
  • Promoter Regions, Genetic
  • Semiconductors
  • Sequence Analysis, DNA / instrumentation
  • Sequence Analysis, DNA / methods*

Substances

  • DNA