title: RNF43 is a tumour suppressor gene mutated in mucinous tumours of the ovary.
abstract: Mucinous carcinomas represent a distinct morphological subtype which can arise from several organ sites, including the ovary, and their genetic characteristics are largely under-described. Exome sequencing of 12 primary mucinous ovarian tumours identified RNF43 as the most frequently somatically mutated novel gene, secondary to KRAS and mutated at a frequency equal to that of TP53 and BRAF. Further screening of RNF43 in a larger cohort of ovarian tumours identified additional mutations, with a total frequency of 2/22 (9%) in mucinous ovarian borderline tumours and 6/29 (21%) in mucinous ovarian carcinomas. Seven mutations were predicted to truncate the protein and one missense mutation was predicted to be deleterious by in silico analysis. Six tumours had allelic imbalance at the RNF43 locus, with loss of the wild-type allele. The mutation spectrum strongly suggests that RNF43 is an important tumour suppressor gene in mucinous ovarian tumours, similar to its reported role in mucinous pancreatic precancerous cysts.
authors.affiliation: Victorian Breast Cancer Research Consortium (VBCRC), Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Georgina L
authors.initials: GL
authors.lastname: Ryland
authors.forename: Sally M
authors.initials: SM
authors.lastname: Hunter
authors.forename: Maria A
authors.initials: MA
authors.lastname: Doyle
authors.forename: Simone M
authors.initials: SM
authors.lastname: Rowley
authors.forename: Michael
authors.initials: M
authors.lastname: Christie
authors.forename: Prue E
authors.initials: PE
authors.lastname: Allan
authors.forename: David D L
authors.initials: DD
authors.lastname: Bowtell
authors.forename: Kylie L
authors.initials: KL
authors.lastname: Gorringe
authors.forename: Ian G
authors.initials: IG
authors.lastname: Campbell
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology; D003198:Computer Simulation; D018291:Cystadenoma, Mucinous / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D059472:Exome / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA; D044767:Ubiquitin-Protein Ligases
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D015513:Oncogene Proteins; C496945:RNF43 protein, human; D044767:Ubiquitin-Protein Ligases