title: Molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes.
abstract: OBJECTIVE
  Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities with the well-established intrinsic molecular subtypes of breast cancer.
  
  
  METHODS
  Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published gene profiles for the ovarian and breast cancer subtypes. Correlations to gene expression modules representing key biological breast cancer features were also sought. Validation was performed using an independent, publicly available dataset.
  
  
  RESULTS
  5,944 genes were significantly differentially expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal-like breast cancer subtype were found. The benign and borderline serous tumors together were significantly correlated to the normal-like breast cancer subtype and the ovarian cancer signature derived from borderline tumors. The borderline tumors in the study dataset, in addition, also correlated significantly to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged.
  
  
  CONCLUSIONS
  These data link the transcriptional profiles of serous ovarian cancer to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and basal-like breast cancer, and suggest that biomarkers and targeted therapies may overlap between these tumor subsets. The link between benign and borderline ovarian cancer and luminal breast cancer may indicate endocrine responsiveness in a subset of ovarian cancers.
authors.affiliation: Division of Oncology-Pathology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: Jenny-Maria
authors.initials: JM
authors.lastname: Jönsson
authors.affiliation: Division of Oncology-Pathology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden; CREATE Health Strategic Center for Translational Cancer Research, Lund University, Lund, Sweden.
authors.forename: Ida
authors.initials: I
authors.lastname: Johansson
authors.affiliation: Division of Oncology-Pathology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden; Clinical Research Centre, Hvdiovre Hospital, Copenhagen University, Hvidovre, Denmark.
authors.forename: Mev
authors.initials: M
authors.lastname: Dominguez-Valentin
authors.affiliation: Division of Oncology-Pathology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden; CREATE Health Strategic Center for Translational Cancer Research, Lund University, Lund, Sweden.
authors.forename: Siker
authors.initials: S
authors.lastname: Kimbung
authors.affiliation: Division of Oncology-Pathology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Jönsson
authors.affiliation: Department of Pathology, Clinical Research Centre, Hvidovre Hospital, Copenhagen University, Hvidovre, Denmark.
authors.forename: Jesper Hansen
authors.initials: JH
authors.lastname: Bonde
authors.affiliation: Division of Obstetrics and Gynecology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: Päivi
authors.initials: P
authors.lastname: Kannisto
authors.affiliation: Division of Oncology-Pathology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Måsbäck
authors.affiliation: Division of Oncology-Pathology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Malander
authors.affiliation: Division of Oncology-Pathology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden; Clinical Research Centre, Hvdiovre Hospital, Copenhagen University, Hvidovre, Denmark.
authors.forename: Mef
authors.initials: M
authors.lastname: Nilbert
authors.affiliation: Division of Oncology-Pathology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden; CREATE Health Strategic Center for Translational Cancer Research, Lund University, Lund, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hedenfalk
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D016000:Cluster Analysis; D018293:Cystadenoma, Serous / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D015203:Reproducibility of Results
chemical_list: D048493:Proto-Oncogene Proteins B-raf