title: RNF43 mutations are recurrent in Chinese patients with mucinous ovarian carcinoma but absent in other subtypes of ovarian cancer.
abstract: Ring finger protein 43 (RNF43) is an E3 ubiquitin-protein ligase that accepts ubiquitin from an E2 ubiquitin-conjugating enzyme and directly transfers the ubiquitin to targeted substrate proteins. Recently, large-scale sequencing efforts have identified prevalent RNF43 mutations in pancreatic and ovarian mucinous carcinomas. In the present study, we sequenced the entire coding sequences of RNF43 in 251 Chinese patients with distinct subtypes of ovarian cancers for the presence of RNF43 mutations. A total of 2 novel heterozygous nonsynonymous RNF43 mutations were identified in 2 out of 15 (13.3%) patients with mucinous ovarian carcinoma, these mutations were evolutionarily highly conserved; while no mutation was detected in other samples. In addition, none of the RNF43-mutated samples harbored DICER1 (dicer 1, ribonuclease type III), PPP2R1A (protein phosphatase 2, regulatory subunit A, alpha), TRRAP (transformation/transcription domain-associated protein) and DNMT3A (DNA (cytosine-5-)-methyltransferase 3 alpha) hot-spot mutations. Recurrent RNF43 mutations existed in mucinous ovarian carcinomas implicated that these mutations might play crucial roles in the tumorigenesis of these patients, while the absence of DICER1, PPP2R1A, TRRAP and DNMT3A hot-spot mutations suggested that these genetic alterations might not play synergistic roles with RNF43 mutations in these individuals. Additionally, the absence of RNF43 mutations in other subtypes of ovarian carcinoma implicated that RNF43 mutations might not be actively involved in the pathogenesis of these disorders.
authors.affiliation: Key Laboratory of Women's Reproductive Health of Jiangxi Province/Central Lab, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zou
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Fa-Ying
authors.initials: FY
authors.lastname: Liu
authors.forename: Mei-Zhen
authors.initials: MZ
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Xiao-Qun
authors.initials: XQ
authors.lastname: Yuan
authors.forename: Ou-Ping
authors.initials: OP
authors.lastname: Huang
authors.forename: Ming
authors.initials: M
authors.lastname: He
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002681:China; D000090205:DNA Methyltransferase 3A; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D016415:Sequence Alignment; D044767:Ubiquitin-Protein Ligases; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C000717967:DNMT3A protein, human; D015513:Oncogene Proteins; D000090205:DNA Methyltransferase 3A; C496945:RNF43 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: A; Arg; Asp; COSMIC; Catalogue of Somatic Mutations in Cancer; Chinese; DICER1; DNA (cytosine-5-)-methyltransferase 3 alpha; DNMT3A; FFPE; G; Ile; Mutation; Ovarian cancer; PCR; PPP2R1A; RNF43; SPSS; Statistical Product and Service Solutions; TCGA; TRRAP; The Cancer Genome Atlas; Val; adenosine; arginine; aspartic acid; dicer 1, ribonuclease type III; formalin-fixed, paraffin-embedded; guanosine; isoleucine; polymerase chain reaction; protein phosphatase 2, regulatory subunit A, alpha; ring finger protein 43; transformation/transcription domain-associated protein; valine