title: Mutational landscape of mucinous ovarian carcinoma and its neoplastic precursors.
abstract: BACKGROUND
  Mucinous ovarian tumors are an unusual group of rare neoplasms with an apparently clear progression from benign to borderline to carcinoma, yet with a controversial cell of origin in the ovarian surface epithelium. They are thought to be molecularly distinct from other ovarian tumors but there have been no exome-level sequencing studies performed to date.
  
  
  METHODS
  To understand the genetic etiology of mucinous ovarian tumors and assess the presence of novel therapeutic targets or pathways, we undertook exome sequencing of 24 tumors encompassing benign (5), borderline (8) and carcinoma (11) histologies and also assessed a validation cohort of 58 tumors for specific gene regions including exons 4-9 of TP53.
  
  
  RESULTS
  The predominant mutational signature was of C>T transitions in a NpCpG context, indicative of deamination of methyl-cytosines. As well as mutations in known drivers (KRAS, BRAF and CDKN2A), we identified a high percentage of carcinomas with TP53 mutations (52 %), and recurrent mutations in RNF43, ELF3, GNAS, ERBB3 and KLF5.
  
  
  CONCLUSIONS
  The diversity of mutational targets suggests multiple routes to tumorigenesis in this heterogeneous group of tumors that is generally distinct from other ovarian subtypes.
authors.affiliation: Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria Australia.
authors.forename: Georgina L
authors.initials: GL
authors.lastname: Ryland
authors.affiliation: Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria Australia.
authors.forename: Sally M
authors.initials: SM
authors.lastname: Hunter
authors.affiliation: Bioinformatics Core Facility, Peter MacCallum Cancer Centre, East Melbourne, Victoria Australia.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Doyle
authors.affiliation: Bioinformatics Core Facility, Peter MacCallum Cancer Centre, East Melbourne, Victoria Australia.
authors.forename: Franco
authors.initials: F
authors.lastname: Caramia
authors.affiliation: Bioinformatics Core Facility, Peter MacCallum Cancer Centre, East Melbourne, Victoria Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Li
authors.affiliation: Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria Australia.
authors.forename: Simone M
authors.initials: SM
authors.lastname: Rowley
authors.affiliation: Department of Anatomical Pathology, Royal Melbourne Hospital, Parkville, Victoria Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Christie
authors.affiliation: Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne, Victoria Australia.
authors.forename: Prue E
authors.initials: PE
authors.lastname: Allan
authors.affiliation: Centre for Cancer Research, MIMR-PHI Institute of Medical Research, Clayton, Victoria Australia ; Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria Australia ; Epworth Research Institute, Epworth HealthCare, Richmond, Victoria Australia.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Stephens
authors.affiliation: Cancer Genetics and Genomics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria Australia ; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria Australia ; Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria Australia.
authors.forename: David D L
authors.initials: DD
authors.lastname: Bowtell
authors.affiliation: Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria Australia ; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria Australia ; Department of Pathology, University of Melbourne, Parkville, Victoria Australia.
authors.forename: Ian G
authors.initials: IG
authors.lastname: Campbell
authors.affiliation: Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria Australia ; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria Australia ; Department of Pathology, University of Melbourne, Parkville, Victoria Australia.
authors.forename: Kylie L
authors.identifier: 0000-0001-5681-2022
authors.initials: KL
authors.lastname: Gorringe