title: Methylation of Tumor Suppressor Genes in Autoimmune Pancreatitis.
abstract: Autoimmune pancreatitis (AIP) is a representative IgG4-related and inflammatory disease of unknown etiology. To clarify mechanisms of carcinogenesis resulting from AIP, we focused on methylation abnormalities and KRAS mutations in AIP.
  
  
  
  Six tumor suppressor genes (NPTX2, Cyclin D2, FOXE1, TFPI2, ppENK, and p16) that exhibited hypermethylation in pancreatic carcinoma were selected for quantitative SYBR green methylation-specific polymerase chain reaction in 10 AIP specimens, 10 pancreatic adenocarcinoma cases without history of AIP containing carcinoma areas (CAs) and noncarcinoma areas (NCAs), and 11 normal pancreas (NP) samples. KRAS mutation in codons 12, 13, and 61 were also investigated using direct sequencing.
  
  
  
  Hypermethylation events (≥10%) were identified in NPTX2, Cyclin D2, FOXE1, TFPI2, ppENK, and p16 in 1, 2, 2, 0, 2, and 0 CA cases, respectively, but not in these 6 candidate genes in AIP, NCA, and NP. However, the TFPI2 methylation ratio was significantly higher in AIP than NCA and NP. Direct sequencing results for KRAS showed no single-point mutations in AIP.
  
  
  
  These are the first studies characterizing methylation abnormalities in AIP. AIP's inflammatory condition may be related to carcinogenesis. Further study will elucidate methylation abnormalities associated with carcinogenesis in AIP.
authors.affiliation: From the *Department of Laboratory Medicine, and †Department of Gastroenterology, Shinshu University School of Medicine; ‡Center for Health, Safety, and Environmental Management, Shinshu University; §Department of Pathology, Aizawa Hospital, Matsumoto; ∥Department of Pathology, Nagano Municipal Hospital, Nagano; ¶Department of Pathology, Saku Central Hospital, Saku; and #Department of Biomedical Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kinugawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Uehara
authors.forename: Kenji
authors.initials: K
authors.lastname: Sano
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Matsuda
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Maruyama
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nakajima
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hamano
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kawa
authors.forename: Kayoko
authors.initials: K
authors.lastname: Higuchi
authors.forename: Noriko
authors.initials: N
authors.lastname: Hosaka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shiozawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ishigame
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Ota
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics; D010195:Pancreatitis / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)