title: Diagnosis and prognostication of ductal adenocarcinomas of the pancreas based on genome-wide DNA methylation profiling by bacterial artificial chromosome array-based methylated CpG island amplification.
abstract: To establish diagnostic criteria for ductal adenocarcinomas of the pancreas (PCs), bacterial artificial chromosome (BAC) array-based methylated CpG island amplification was performed using 139 tissue samples. Twelve BAC clones, for which DNA methylation status was able to discriminate cancerous tissue (T) from noncancerous pancreatic tissue in the learning cohort with a specificity of 100%, were identified. Using criteria that combined the 12 BAC clones, T-samples were diagnosed as cancers with 100% sensitivity and specificity in both the learning and validation cohorts. DNA methylation status on 11 of the BAC clones, which was able to discriminate patients showing early relapse from those with no relapse in the learning cohort with 100% specificity, was correlated with the recurrence-free and overall survival rates in the validation cohort and was an independent prognostic factor by multivariate analysis. Genome-wide DNA methylation profiling may provide optimal diagnostic markers and prognostic indicators for patients with PCs.
authors.affiliation: Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Gotoh
authors.forename: Eri
authors.initials: E
authors.lastname: Arai
authors.forename: Saori
authors.initials: S
authors.lastname: Wakai-Ushijima
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hiraoka
authors.forename: Tomoo
authors.initials: T
authors.lastname: Kosuge
authors.forename: Fumie
authors.initials: F
authors.lastname: Hosoda
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Shibata
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Sana
authors.initials: S
authors.lastname: Yokoi
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.forename: Yae
authors.initials: Y
authors.lastname: Kanai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000235:genetics*; D022202:Chromosomes, Artificial, Bacterial; D015331:Cohort Studies; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D005784:Gene Amplification; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity