title: Role of KRAS and BRAF gene mutations in mucinous ovarian carcinoma.
abstract: OBJECTIVE
  The goals of this study were to perform a comprehensive assessment of the prevalence of KRAS oncogene mutations in invasive epithelial ovarian carcinomas of various histologic subtypes, and for any subgroup(s) in which KRAS mutation was found to be common, to address the hypothesis that those tumors without KRAS mutation had sustained alternative activation of this signaling pathway through mutation of the BRAF oncogene.
  
  
  METHODS
  A total of 104 primary, invasive epithelial ovarian carcinomas from a 10-year period at this institution were selected for study based on histologic classification. The histologic cell type was serous in 21 cases, endometrioid in 30 cases, clear cell in 31 cases, and mucinous in 22 cases. Additional clinical and pathological information was abstracted from patient records, and pathology review was performed for all cases. Direct sequence analysis of exon 2 of the KRAS gene, containing codon 12, was performed using DNA isolated from all tumor specimens. Sequence analyses of exons 11 and 15 of the BRAF gene were performed for the 22 cases of mucinous ovarian carcinoma.
  
  
  RESULTS
  Activating KRAS mutations were more common in mucinous tumors (50%) than in all other histologic types combined (5%; P < 10(-7)). Mutation of KRAS was more common in stage I tumors than in advanced stage tumors (P = 0.0004). Of the 11 mucinous tumors with KRAS mutations, 6 were of Mullerian (endocervical) type and 5 were of gastrointestinal type. No mucinous tumor was found to harbor a BRAF mutation.
  
  
  CONCLUSIONS
  These data indicate that KRAS oncogene mutations exist in several histologic types of invasive epithelial ovarian carcinoma, especially stage I tumors, but are common only in tumors of mucinous histology. Mutations are equally prevalent in mucinous ovarian cancers of Müllerian and gastrointestinal types. In contrast to other solid tumor types frequently affected by KRAS mutation, mucinous ovarian cancers without a KRAS mutation have not sustained alternative activation of this signaling pathway through mutation of the BRAF oncogene.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Gemignani
authors.forename: Alan C
authors.initials: AC
authors.lastname: Schlaerth
authors.forename: Faina
authors.initials: F
authors.lastname: Bogomolniy
authors.forename: Richard R
authors.initials: RR
authors.lastname: Barakat
authors.forename: Oscar
authors.initials: O
authors.lastname: Lin
authors.forename: Robert
authors.initials: R
authors.lastname: Soslow
authors.forename: Ennapandam
authors.initials: E
authors.lastname: Venkatraman
authors.forename: Jeff
authors.initials: J
authors.lastname: Boyd
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf
chemical_list: D015513:Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf