title: Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC.
abstract: BACKGROUND PROMOTER: hypermethylation plays a major role in cancer through transcriptional silencing of critical genes. The aim of our study is to evaluate the methylation status of these genes in the colonic mucosa without dysplasia or adenocarcinoma at the different steps of sporadic and UC-related carcinogenesis and to investigate the possible role of genomic methylation as a marker of CRC.
  
  
  RESULTS
  The expression of Dnmts 1 and 3A was significantly increased in UC-related carcinogenesis compared to non inflammatory colorectal carcinogenesis. In non-neoplastic colonic mucosa, the number of methylated genes resulted significantly higher in patients with CRC and in those with UC-related CRC compared to the HC and UC patients and patients with dysplastic lesion of the colon. The number of methylated genes in non-neoplastic colonic mucosa predicted the presence of CRC with good accuracy either in non inflammatory and inflammatory related CRC.
  
  
  METHODS
  Colonic mucosal samples were collected from healthy subjects (HC) (n = 30) and from patients with ulcerative colitis (UC) (n = 29), UC and dysplasia (n = 14), UC and cancer (n = 10), dysplastic adenoma (n = 14), and colon adenocarcinoma (n = 10). DNA methyltransferases-1, -3a, -3b, mRNA expression were quantified by real time qRT-PCR. The methylation status of CDH13, APC, MLH1, MGMT1 and RUNX3 gene promoters was assessed by methylation-specific PCR.
  
  
  CONCLUSIONS
  Methylation status of APC, CDH13, MGMT, MLH1 and RUNX3 in the non-neoplastic mucosa may be used as a marker of CRC: these preliminary results could allow for the adjustment of a patient's surveillance interval and to select UC patients who should undergo intensive surveillance.
authors: Surgical Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy.
authors: Marco
authors: M
authors: Scarpa
authors: Surgical Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy.
authors: Melania
authors: M
authors: Scarpa
authors: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors: Ignazio
authors: I
authors: Castagliuolo
authors: Department of Surgery Oncology and Gastroenterology DISCOG, University of Padova, Padova, Italy.
authors: Francesca
authors: F
authors: Erroi
authors: Surgical Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy.
authors: Andromachi
authors: A
authors: Kotsafti
authors: Department of Surgery Oncology and Gastroenterology DISCOG, University of Padova, Padova, Italy.
authors: Silvia
authors: S
authors: Basato
authors: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors: Paola
authors: P
authors: Brun
authors: Department of Surgery Oncology and Gastroenterology DISCOG, University of Padova, Padova, Italy.
authors: Renata
authors: R
authors: D'Incà
authors: Department of Medicine, University of Padova, Padova, Italy.
authors: Massimo
authors: M
authors: Rugge
authors: Department of Surgery Oncology and Gastroenterology DISCOG, University of Padova, Padova, Italy.
authors: Imerio
authors: I
authors: Angriman
authors: Surgical Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy.
authors: Carlo
authors: C
authors: Castoro
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015820:Cadherins / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000473:pathology; D003106:Colon / Q000473:pathology*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000096:biosynthesis / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1 / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins / Q000235:genetics; D055815:Young Adult; D000097584:DNA Methyltransferase 3B
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D014408:Biomarkers, Tumor; D015820:Cadherins; D050677:Core Binding Factor Alpha 3 Subunit; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D015254:DNA Modification Methylases; D045643:DNA Repair Enzymes; D000070957:MutL Protein Homolog 1; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D000097584:DNA Methyltransferase 3B; C555337:APC protein, human; C000717967:DNMT3A protein, human; C099972:H-cadherin; C501486:MLH1 protein, human; C493729:Runx3 protein, human; C515491:MGMT protein, human
keywords: APC; biomarker; colorectal cancer; promoter methylation; ulcerative colitis