title: High-throughput mutation profiling in intraductal papillary mucinous neoplasm (IPMN).
abstract: BACKGROUND
  Specific mutations leading to the development of various histological grades of intraductal papillary mucinous neoplasm (IPMN) have been partially characterized.
  
  
  METHODS
  Analysis of 323 oncogenic mutations in 22 tumor-related genes was conducted, using a chip-based matrix-assisted laser desorption time-of-flight mass spectrometer of DNA extracted from microdissected cells of low-grade (n = 14), borderline (n = 6), and invasive IPMN (n = 7). Additional assays were performed on the DNA extracted from dyplastic cells found in the background of the adenocarcinoma.
  
  
  RESULTS
  We identified 9 K-ras mutations (low grade, 2/14; borderline, 1/6; invasive, 6/7), 3 p53 mutations (low grade, 1/14; invasive 2/7), and 2 PIK3CA mutations (low grade, 1/14; invasive, 1/7). K-ras, p53, and PIK3CA mutations present in the invasive cancer were absent in the adjacent precursor cells in 50% of the cases. In one patient, K-ras mutation was present in the precursor lesion and absent in the adjacent invasive lesion.
  
  
  CONCLUSIONS
  Of the 22 screened tumor-related genes, only K-ras, p53, and PIK3CA mutations were found in IPMN. K-ras mutations are more prevalent in invasive than premalignant IPMN. The variable coexistence of mutations in the invasive cancer and in the adjacent precursor cells may point to the heterogeneous nature of this tumor.
authors.affiliation: Department of Surgery B, Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel-Aviv University, 6 Weitzman St., Tel Aviv 64239, Israel. nirl@tasmc.health.gov.il
authors.forename: Nir
authors.initials: N
authors.lastname: Lubezky
authors.forename: Menahem
authors.initials: M
authors.lastname: Ben-Haim
authors.forename: Sylvia
authors.initials: S
authors.lastname: Marmor
authors.forename: Eli
authors.initials: E
authors.lastname: Brazowsky
authors.forename: Gideon
authors.initials: G
authors.lastname: Rechavi
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Klausner
authors.forename: Yoram
authors.initials: Y
authors.lastname: Cohen
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology; D000231:Adenocarcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D005260:Female; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D011905:Genes, ras; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011379:Prognosis
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human