title: FOXE1 and SYNE1 genes hypermethylation panel as promising biomarker in colitis-associated colorectal neoplasia.
abstract: BACKGROUND
  Colitis-associated colorectal cancer affects individuals with inflammatory bowel disease (IBD) more often and earlier than cancer in the general population. Colonoscopy provides the surveillance gold standard. Changes to the surveillance intervals depending on endoscopic activity have been made, given data demonstrating that this is an important predictor of future dysplasia or cancer, but adjuvant, noninvasive clinical tools are still warranted to improve surveillance outcomes and to assist in management and interpretation of dysplasia. Methylation markers may be able to do this.
  
  
  METHODS
  SYNE1, FOXE1, NDRG4, and PHACTR3 genes were screened using methylation-specific PCR that permit the methylation status of the genes to be determined directly on biopsies. Ninety-three patients with long-standing IBD undergoing a cancer surveillance program, and 30 healthy controls were studied. These included colorectal adenocarcinomas on a background of IBD of various stages (n = 25), IBD-associated dysplastic lesions (n = 29), adenomas arising on a background of ulcerative colitis (n = 8), samples from patients with no evidence of dysplasia or cancer but long-standing IBD (n = 31), and symptomatic patients found to have normal colonoscopy (controls) (n = 30).
  
  
  RESULTS
  Gene promotor hypermethylation of SYNE1 and FOXE1 genes varied significantly between the groups and was increasingly likely with increased disease severity. Neither occurred in controls, whereas promotor hypermethylation was detected in biopsies of 60% of patients with colitis-associated colorectal cancer for FOXE1 and 80% for SYNE1. Promotor hypermethylation of either gene was highly significantly different between the groups overall.
  
  
  CONCLUSIONS
  FOXE1 and SYNE1 hypermethylation markers demonstrated significantly increased expression in neoplastic tissue. Promoter methylation analysis of these genes might be a useful marker of neoplasia in long-standing IBD.
authors.affiliation: *Gastroenterology, University College Hospital, London, United Kingdom; †Gastroenterology, Parma University Hospital, Parma, Italy; ‡Research and Development, MDxHealth SA, Liege, Belgium; §Department of Surgery, Parma University Hospital, Parma Italy; ‖Department of Pathology, University College London, London, United Kingdom; ¶Department of Pathology, University of Parma, Parma, Italy; **Statsconsultancy Ltd, Amersham, United Kingdom; ††Department of Pathology, University of Oxford, Oxford, United Kingdom; and ‡‡Surgery and Cancer, Imperial College, London, United Kingdom.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Papadia
authors.forename: Joost
authors.initials: J
authors.lastname: Louwagie
authors.forename: Paolo
authors.initials: P
authors.lastname: Del Rio
authors.forename: Madeleine
authors.initials: M
authors.lastname: Grooteclaes
authors.forename: Alessandro
authors.initials: A
authors.lastname: Coruzzi
authors.forename: Chiara
authors.initials: C
authors.lastname: Montana
authors.forename: Marco
authors.initials: M
authors.lastname: Novelli
authors.forename: Cesare
authors.initials: C
authors.lastname: Bordi
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: de' Angelis
authors.forename: Paul
authors.initials: P
authors.lastname: Bassett
authors.forename: Joseph
authors.initials: J
authors.lastname: Bigley
authors.forename: Bryan
authors.initials: B
authors.lastname: Warren
authors.forename: Wendy
authors.initials: W
authors.lastname: Atkin
authors.forename: Alastair
authors.initials: A
authors.lastname: Forbes
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D003092:Colitis / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D003598:Cytoskeletal Proteins; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; C106894:FOXE1 protein, human; D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C415465:SYNE1 protein, human