Identification of Methylation Profiles of Cancer-related Genes in Circulating Tumor Cells Population

Anticancer Res. 2017 Mar;37(3):1105-1112. doi: 10.21873/anticanres.11423.

Abstract

Background: We performed an epigenetic analysis of the first exon of the hVIM gene and the SFRP2 in circulating tumor cells (CTCs) and correlation with the corresponding primary colorectal cancer (CRC) tissue.

Patients and methods: CTCs detection in 52 colorectal cancer patients was managed by a multi-marker immunomagnetic method with the use of quantum dots (QDs). To determine methylation levels we used high-resolution melting (HRM) technology.

Results: In the case of VIM we found 76.9% methylated samples, compared to 53.8% in tissue samples. Regarding SFRP2 promoter methylation levels in tissue and CTCs samples, 67.3% and 73.1%, were found methylated respectively. Correlation analysis of methylation levels with KRAS and BRAF mutations (performed in our previous study) demonstrates that high-methylation epigenotype strongly correlates to BRAF mutation.

Conclusion: CTCs is a promising diagnostic tool. The combination of genetic mutations and epigenetic aberrations specifically in CTCs, will ameliorate CRC diagnosis in the future.

Keywords: CTCs; CTCs isolation; colorectal cancer; methylation profile; molecular characterization; quantum dots.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Chromosome Aberrations
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / genetics*
  • DNA Methylation*
  • Epigenesis, Genetic
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Neoplastic Cells, Circulating*
  • Oligonucleotide Array Sequence Analysis
  • Oncogenes
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Quantum Dots

Substances

  • KRAS protein, human
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)