title: Molecular alterations in colitis-associated colorectal neoplasia: study from a low prevalence area using magnifying chromo colonoscopy.
abstract: OBJECTIVE
  Longstanding ulcerative colitis (UC) predisposes to colorectal cancer (CRC). To understand the molecular pathogenesis of colitis-associated colorectal neoplasia (UC-CRN), we studied the frequency of microsatellite instability (MSI) and mutations in p53, BRAF and KRAS genes in the tissues of patients with long standing UC with or without neoplasia and compared them with colitis patients without risk of neoplasia, and those with sporadic colorectal neoplasia (S-CRN) in an area with lower prevalence for either disease.
  
  
  METHODS
  Biopsies were obtained during magnifying chromo colonoscopy or routine colonoscopy in consecutive UC patients with high risk (UC-HR) and low risk (UC-LR) of neoplasia, and those with S-CRN. MSI (NCI-Bethesda panel) and mutations in p53, KRAS and BRAF genes were analysed.
  
  
  RESULTS
  Twenty-eight patients with UC-HR, 30 with UC-LR and 30 with S-CRN were included. Six (21.4%) of UC-HR had neoplasia (Progressors). MSI was not detected in the UC-CRN group as compared to 5 (16.7%) in the S-CRN group. p53 mutations occurred in 1 (3.3%) of UC-LR, increasing to 6 (27.3%, P<0.05) and 3 (50%, P<0.05) in the UC-HR subgroups without and with neoplasia respectively, as against 10 (33.3%) in sporadic neoplasia group. KRAS mutations were found only in the presence of neoplasia. None showed the BRAF mutation.
  
  
  CONCLUSIONS
  In a population with a lower prevalence for UC and CRC, the molecular pathogenesis of colitis-associated colorectal neoplasia is comparable to that reported from areas with a higher prevalence of these diseases, MSI being an exception.
authors.affiliation: Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal University, Manipal 576 104, India.
authors.forename: Bhadravathi Marigowda
authors.initials: BM
authors.lastname: Shivakumar
authors.forename: Balasubramanian Lakshman
authors.initials: BL
authors.lastname: Kumar
authors.forename: Ganesh
authors.initials: G
authors.lastname: Bhat
authors.forename: Deepak
authors.initials: D
authors.lastname: Suvarna
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Rao
authors.forename: C Ganesh
authors.initials: CG
authors.lastname: Pai
authors.forename: Kapaettu
authors.initials: K
authors.lastname: Satyamoorthy
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D000236:Adenoma / Q000453:epidemiology / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D003113:Colonoscopy / Q000379:methods; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D016158:Genes, p53; D005819:Genetic Markers; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012306:Risk; D018631:ras Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins