title: PIK3CA mutations in mucinous cystic neoplasms of the pancreas.
abstract: OBJECTIVE
  Mucinous cystic neoplasms (MCNs) are rare, potentially curable, mucin-producing neoplasms of the pancreas. We have previously reported PIK3CA (phosphoinositide-3-kinase catalytic subunit, p110α) mutations in intraductal papillary mucinous neoplasms, another mucin-producing neoplasm of the pancreas. In this study, we analyzed the presence of PIK3CA and AKT1/PKB (V-akt murine thymoma viral oncogene homolog 1) hot-spot mutations in MCN specimens.
  
  
  METHODS
  Using the genomic DNA sequencing of tumor tissues isolated by laser capture microdissection, we evaluated 15 well-characterized MCNs for the E542K, E545K (exon 9), and H1047R (exon 20) hot-spot mutations in the PIK3CA gene and the E17K mutation in the AKT1 gene.
  
  
  RESULTS
  A hot-spot mutation (E545K) of the PIK3CA gene was detected in 1 of the 15 MCNs and further confirmed by a mutant-enriched method. Interestingly, this mutation was found to be present only in the high-grade but not in low-grade dysplastic epithelium obtained from this neoplasm and coexisted with a KRAS mutation. No mutations were identified in the AKT1 gene.
  
  
  CONCLUSIONS
  Our data, when combined with previous reports on intraductal papillary mucinous neoplasms, indicate that oncogenic activation of the PI3K pathway involving PIK3CA gene mutations can contribute to the progression of mucin-producing neoplasms but not pancreatic intraepithelial neoplasia. PIK3CA status could be useful for understanding their progression to malignancy.
authors: From the *Department of Pathology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY; †Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD; ‡Department of Otolaryngology/Head and Neck Surgery, Columbia University Medical Center; and §Department of Otolaryngology/Head and Neck Surgery, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY.
authors: Dario
authors: D
authors: Garcia-Carracedo
authors: Zong-Ming
authors: ZM
authors: Chen
authors: Wanglong
authors: W
authors: Qiu
authors: Alicia S
authors: AS
authors: Huang
authors: Sophia M
authors: SM
authors: Tang
authors: Ralph H
authors: RH
authors: Hruban
authors: Gloria H
authors: GH
authors: Su
mesh_terms: D000328:Adult; D000368:Aged; D058534:Class I Phosphatidylinositol 3-Kinases; D018282:Cystadenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051057:Proto-Oncogene Proteins c-akt; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins