title: Whole exome sequence analysis of serous borderline tumors of the ovary.
abstract: OBJECTIVE
  Serous borderline tumor (SBT) is a unique histopathologic entity of the ovary, believed to be intermediate between benign cystadenoma and invasive low-grade serous carcinoma. While somatic mutations in the KRAS or BRAF, and rarely ERBB2, genes have been well characterized in SBTs, other genetic alterations have not been described. Toward a more comprehensive understanding of the molecular genetic architecture of SBTs, we undertook whole exome sequencing of this tumor type.
  
  
  METHODS
  Following pathologic review and laser capture microdissection to enrich for tumor cells, whole exomes were prepared from DNA of two independent SBTs and subjected to massively parallel DNA sequencing.
  
  
  RESULTS
  Both tumors contained an activating mutation of the BRAF gene. A total of 15 additional somatic mutations were identified, nine in one tumor and six in the other. Eleven were missense mutations and four were nonsense or deletion mutations. Fourteen of the 16 genes found to be mutated in this study have been reported to be mutated in other cancers. Furthermore, 12 of these genes are mutated in ovarian cancers. The FBXW7 and KIAA1462 genes are noteworthy candidates for a pathogenic role in serous borderline tumorigenesis.
  
  
  CONCLUSIONS
  These findings suggest that a very small number of somatic genetic mutations are characteristic of SBTs of the ovary, thus supporting their classification as a relatively genetically stable tumor type. The mutant genes described herein represent novel candidates for the pathogenesis of ovarian SBT.
authors.affiliation: Cancer Genome Institute, Fox Chase Cancer Center, 333 Cottman Ave., Philadelphia, PA 19111, USA. jeff.boyd@fccc.edu
authors.forename: Jeff
authors.initials: J
authors.lastname: Boyd
authors.forename: Biao
authors.initials: B
authors.lastname: Luo
authors.forename: Suraj
authors.initials: S
authors.lastname: Peri
authors.forename: Beth
authors.initials: B
authors.lastname: Wirchansky
authors.forename: Lucinda
authors.initials: L
authors.lastname: Hughes
authors.forename: Caitlin
authors.initials: C
authors.lastname: Forsythe
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
mesh_terms: D015815:Cell Adhesion Molecules / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D018293:Cystadenoma, Serous / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D044783:F-Box Proteins / Q000235:genetics; D000073979:F-Box-WD Repeat-Containing Protein 7; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; C000632511:JCAD protein, human; D044767:Ubiquitin-Protein Ligases; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: Exome; Gene; Mutation; Ovarian; Serous borderline tumor