title: Novel methylation panel for the early detection of neoplasia in high-risk ulcerative colitis and Crohn's colitis patients.
abstract: BACKGROUND
  Patients with ulcerative colitis and Crohn's colonic disease are at increased risk of developing colorectal cancer (CRC). The aim of the study was to analyze the methylation status of selected genes as a risk marker for CRC in inflammatory bowel disease (IBD) patients.
  
  
  METHODS
  We evaluated the methylation status of four genes (TGFB2, SLIT2, HS3ST2, and TMEFF2) in biopsies of four groups of patients: 60 patients with sporadic CRC, 32 patients with IBD-associated neoplasia, 85 patients with IBD without associated neoplasia (20 at high risk and 65 at low risk), and 28 healthy controls. Methylation-specific melting curve analysis (MS-MCA) was used. Methylation status of these genes was also assessed in stool DNA from 60 IBD patients without neoplasia.
  
  
  RESULTS
  Methylation of the panel of genes analyzed was a very common phenomenon (78%) in IBD-associated neoplasia. The prevalence of methylation in adjacent nonneoplastic mucosa was also high (12/30). This prevalence was higher than in mucosa from healthy controls (2/28;7.1%; P < 0.05). Methylation of SLIT2 and TMEFF2 was more frequently detected in the mucosa of IBD patients at high risk of dysplasia or cancer (15/20) than patients at low risk (32/63) (P = 0.05 and P = 0.03, respectively). When stool samples were assessed, only SLIT2 gene methylation was more frequently methylated in the group of patients at high risk of dysplasia or cancer (4/16) compared to low risk (0/37) (P = 0.006).
  
  
  CONCLUSIONS
  Analysis of a panel of methylation markers may help in the early identification of colorectal dysplasia or cancer in high-risk IBD patients.
authors.affiliation: Translational Research Laboratory, Catalan Institute of Oncology, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Azuara
authors.forename: Francisco
authors.initials: F
authors.lastname: Rodriguez-Moranta
authors.forename: Javier
authors.initials: J
authors.lastname: de Oca
authors.forename: Xavier
authors.initials: X
authors.lastname: Sanjuan
authors.forename: Jordi
authors.initials: J
authors.lastname: Guardiola
authors.forename: Triana
authors.initials: T
authors.lastname: Lobaton
authors.forename: Alex
authors.initials: A
authors.lastname: Wang
authors.forename: Jaume
authors.initials: J
authors.lastname: Boadas
authors.forename: Marta
authors.initials: M
authors.lastname: Piqueras
authors.forename: David
authors.initials: D
authors.lastname: Monfort
authors.forename: Sara
authors.initials: S
authors.lastname: Galter
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
authors.forename: Victor
authors.initials: V
authors.lastname: Moreno
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capellá
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000150:complications* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000209:etiology; D003424:Crohn Disease / Q000150:complications* / Q000235:genetics; D004247:DNA / Q000235:genetics; D019175:DNA Methylation; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D053781:Transforming Growth Factor beta2 / Q000235:genetics; D000098552:Slit Homolog 2 Protein
chemical_list: D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C509041:TGFB2 protein, human; C423567:TMEFF2 protein, human; D053781:Transforming Growth Factor beta2; D004247:DNA; D000098552:Slit Homolog 2 Protein