title: High-throughput mutation profiling of primary and metastatic endometrial cancers identifies KRAS, FGFR2 and PIK3CA to be frequently mutated.
abstract: BACKGROUND
  Despite being the most common pelvic gynecologic malignancy in industrialized countries, no targeted therapies are available for patients with metastatic endometrial carcinoma. In order to improve treatment, underlying molecular characteristics of primary and metastatic disease must be explored.
  
  
  RESULTS
  We utilized the mass spectrometric-based mutation detection technology OncoMap to define the types and frequency of point somatic mutations in endometrial cancer. 67 primary tumors, 15 metastases corresponding to 7 of the included primary tumors and 11 endometrial cancer cell lines were screened for point mutations in 28 known oncogenes. We found that 27 (40.3%) of 67 primary tumors harbored one or more mutations with no increase in metastatic lesions. FGFR2, KRAS and PIK3CA were consistently the most frequently mutated genes in primary tumors, metastatic lesions and cell lines.
  
  
  CONCLUSIONS
  Our results emphasize the potential for targeting FGFR2, KRAS and PIK3CA mutations in endometrial cancer for development of novel therapeutic strategies.
authors.affiliation: Department of Clinical Medicine, University of Bergen, Bergen, Norway. camilla.krakstad@med.uib.no
authors.forename: Camilla
authors.initials: C
authors.lastname: Krakstad
authors.forename: Even
authors.initials: E
authors.lastname: Birkeland
authors.forename: Danila
authors.initials: D
authors.lastname: Seidel
authors.forename: Kanthida
authors.initials: K
authors.lastname: Kusonmano
authors.forename: Kjell
authors.initials: K
authors.lastname: Petersen
authors.forename: Siv
authors.initials: S
authors.lastname: Mjøs
authors.forename: Erling A
authors.initials: EA
authors.lastname: Hoivik
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Wik
authors.forename: Mari Kyllesø
authors.initials: MK
authors.lastname: Halle
authors.forename: Anne M
authors.initials: AM
authors.lastname: Øyan
authors.forename: Karl-Henning
authors.initials: KH
authors.lastname: Kalland
authors.forename: Henrica Maria Johanna
authors.initials: HM
authors.lastname: Werner
authors.forename: Jone
authors.initials: J
authors.lastname: Trovik
authors.forename: Helga
authors.initials: H
authors.lastname: Salvesen
mesh_terms: D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000556:secondary; D045744:Cell Line, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D016000:Cluster Analysis; D004252:DNA Mutational Analysis; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D008040:Genetic Linkage; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D020125:Mutation, Missense; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D059467:Transcriptome; 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; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins