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

Content Provider	Springer Nature Link
Author	Patai, Árpád V. Barták, Barbara Kinga Péterfia, Bálint Micsik, Tamás Horváth, Réka Sumánszki, Csaba Péter, Zoltán Patai, Árpád Valcz, Gábor Kalmár, Alexandra Tóth, Kinga Krenács, Tibor Tulassay, Zsolt Molnár, Béla
Copyright Year	2016
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.
Starting Page	589
Ending Page	594
Page Count	6
File Format	PDF
ISSN	12194956
Journal	Pathology & Oncology Research
Volume Number	23
Issue Number	3
e-ISSN	15322807
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-11-29
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Biomarker DNA methylation Mutation Serrated polyp Sessile serrated adenoma Traditional serrated adenoma Cancer Research Oncology Pathology Immunology Biomedicine
Content Type	Text
Resource Type	Article
Subject	Cancer Research Pathology and Forensic Medicine Oncology

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