title: MicroRNA genes and their target 3'-untranslated regions are infrequently somatically mutated in ovarian cancers.
abstract: MicroRNAs are key regulators of gene expression and have been shown to have altered expression in a variety of cancer types, including epithelial ovarian cancer. MiRNA function is most often achieved through binding to the 3'-untranslated region of the target protein coding gene. Mutation screening using massively-parallel sequencing of 712 miRNA genes in 86 ovarian cancer cases identified only 5 mutated miRNA genes, each in a different case. One mutation was located in the mature miRNA, and three mutations were predicted to alter the secondary structure of the miRNA transcript. Screening of the 3'-untranslated region of 18 candidate cancer genes identified one mutation in each of AKT2, EGFR, ERRB2 and CTNNB1. The functional effect of these mutations is unclear, as expression data available for AKT2 and EGFR showed no increase in gene transcript. Mutations in miRNA genes and 3'-untranslated regions are thus uncommon in ovarian cancer.
authors.affiliation: Victorian Breast Cancer Research Consortium Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Georgina L
authors.initials: GL
authors.lastname: Ryland
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Bearfoot
authors.forename: Maria A
authors.initials: MA
authors.lastname: Doyle
authors.forename: Samantha E
authors.initials: SE
authors.lastname: Boyle
authors.forename: David Y H
authors.initials: DY
authors.lastname: Choong
authors.forename: Simone M
authors.initials: SM
authors.lastname: Rowley
authors.forename: Richard W
authors.initials: RW
authors.lastname: Tothill
authors.forename: Kylie L
authors.initials: KL
authors.lastname: Gorringe
authors.forename: Ian G
authors.initials: IG
authors.lastname: Campbell
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites / Q000235:genetics; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D066246:ErbB Receptors; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D051176:beta Catenin; C495270:CTNNB1 protein, human; C508053:ERBB2 protein, human; C494921:AKT2 protein, human