Comprehensive DNA Methylation and Mutation Analyses Reveal a Methylation Signature in Colorectal Sessile Serrated Adenomas

Árpád V. Patai, Barbara Kinga Barták, Bálint Péterfia, Tamás Micsik, Réka Horváth, Csaba Sumánszki, Zoltán Péter, Árpád Patai, Gábor Valcz, Alexandra Kalmár, Kinga Tóth, T. Krenács, Z. Tulassay, B. Molnár

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Colorectal sessile serrated adenomas (SSA) are hypothesized to be precursor lesions of an alternative, serrated pathway of colorectal cancer, abundant in genes with aberrant promoter DNA hypermethylation. In our present pilot study, we explored DNA methylation profiles and examined selected gene mutations in SSA. Biopsy samples from patients undergoing screening colonoscopy were obtained during endoscopic examination. After DNA isolation and quality analysis, SSAs (n = 4) and healthy controls (n = 5) were chosen for further analysis. DNA methylation status of 96 candidate genes was screened by q(RT)PCR using Methyl-Profiler PCR array system. Amplicons for 12 gene mutations were sequenced by GS Junior Instrument using ligated and barcoded adaptors. Analysis of DNA methylation revealed 9 hypermethylated genes in both normal and SSA samples. 12 genes (CALCA, DKK2, GALR2, OPCML, PCDH10, SFRP1, SFRP2, SLIT3, SST, TAC1, VIM, WIF1) were hypermethylated in all SSAs and 2 additional genes (BNC1 and PDLIM4) were hypermethylated in 3 out of 4 SSAs, but in none of the normal samples. 2 SSAs exhibited BRAF mutation and synchronous MLH1 hypermethylation and were microsatellite instable by immunohistochemical analysis. Our combined mutation and DNA methylation analysis revealed that there is a common DNA methylation signature present in pre-neoplastic SSAs. This study advocates for the use of DNA methylation as a potential biomarker for the detection of SSA; however, further investigation is needed to better characterize the molecular background of these newly recognized colorectal lesions.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalPathology and Oncology Research
DOIs
Publication statusAccepted/In press - Nov 29 2016

Keywords

  • Biomarker
  • DNA methylation
  • Mutation
  • Serrated polyp
  • Sessile serrated adenoma
  • Traditional serrated adenoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Oncology
  • Cancer Research

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    Patai, Á. V., Barták, B. K., Péterfia, B., Micsik, T., Horváth, R., Sumánszki, C., Péter, Z., Patai, Á., Valcz, G., Kalmár, A., Tóth, K., Krenács, T., Tulassay, Z., & Molnár, B. (Accepted/In press). Comprehensive DNA Methylation and Mutation Analyses Reveal a Methylation Signature in Colorectal Sessile Serrated Adenomas. Pathology and Oncology Research, 1-6. https://doi.org/10.1007/s12253-016-0154-6