title: Frequent mutation of the PIK3CA gene in ovarian and breast cancers.
abstract: OBJECTIVE
  Activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, resulting in increased cell proliferation, survival, and motility, is believed to play an oncogenic role in many cancer types. The PIK3CA gene encodes the p110alpha catalytic subunit of PI3K, and is amplified in some ovarian cancers, whereas the AKT2 gene is amplified in some ovarian, breast, and pancreatic cancers. Recently, in a mutational screen of eight PI3K genes and eight PI3K-like genes, PIK3CA was found to be the only gene affected by somatic mutations, which were observed frequently in gastrointestinal and brain cancers. Here, we test whether PIK3CA is subject to mutation in ovarian and breast cancers.
  
  
  METHODS
  Exons 9 and 20, encoding the highly conserved helical and kinase domains of PIK3CA, were subjected to sequence analysis in 198 advanced stage epithelial ovarian carcinomas and 72 invasive breast carcinomas (48 of ductal histology and 24 of lobular histology).
  
  
  RESULTS
  Somatic missense mutations were observed in 24 of 198 (12%) ovarian carcinomas, and in 13 of 72 (18%) breast carcinomas.
  
  
  CONCLUSIONS
  These data indicate that mutations of PIK3CA play an oncogenic role in substantial fractions of ovarian and breast carcinomas, and in consideration of mutation of other components of the PI3K-AKT pathway in both tumor types, confirm the major oncogenic role of this pathway in ovarian and breast carcinomas.
authors.affiliation: Gynecology and Breast Research Laboratory, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Levine
authors.forename: Faina
authors.initials: F
authors.lastname: Bogomolniy
authors.forename: Cindy J
authors.initials: CJ
authors.lastname: Yee
authors.forename: Alex
authors.initials: A
authors.lastname: Lash
authors.forename: Richard R
authors.initials: RR
authors.lastname: Barakat
authors.forename: Patrick I
authors.initials: PI
authors.lastname: Borgen
authors.forename: Jeff
authors.initials: J
authors.lastname: Boyd
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics*; D020134:Catalytic Domain / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000235:genetics*; D017434:Protein Structure, Tertiary
chemical_list: D004273:DNA, Neoplasm; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human