title: Computational analysis of the mutations in BAP1, PBRM1 and SETD2 genes reveals the impaired molecular processes in renal cell carcinoma.
abstract: Clear cell Renal Cell Carcinoma (ccRCC) is due to loss of von Hippel-Lindau (VHL) gene and at least one out of three chromatin regulating genes BRCA1-associated protein-1 (BAP1), Polybromo-1 (PBRM1) and Set domain-containing 2 (SETD2). More than 350, 700 and 500 mutations are known respectively for BAP1, PBRM1 and SETD2 genes. Each variation damages these genes with different severity levels. Unfortunately for most of these mutations the molecular effect is unknown, so precluding a severity classification. Moreover, the huge number of these gene mutations does not allow to perform experimental assays for each of them. By bioinformatic tools, we performed predictions of the molecular effects of all mutations lying in BAP1, PBRM1 and SETD2 genes. Our results allow to distinguish whether a mutation alters protein function directly or by splicing pattern destruction and how much severely. This classification could be useful to reveal correlation with patients' outcome, to guide experiments, to select the variations that are worth to be included in translational/association studies, and to direct gene therapies.
authors.affiliation: Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche Region, Ancona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Piva
authors.affiliation: Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche Region, Ancona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Giulietti
authors.affiliation: Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche Region, Ancona, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Occhipinti
authors.affiliation: Department of Medical Oncology, AOU Ospedali Riuniti - Polytechnic University of the Marche Region, Ancona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Santoni
authors.affiliation: Department of Medical Oncology, University of Verona, Verona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Massari
authors.affiliation: Department of Medical Oncology, AOU Ospedali Riuniti - Polytechnic University of the Marche Region, Ancona, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Sotte
authors.affiliation: Medical Oncology Unit of Urogenital and Head & Neck Tumors, European Institute of Oncology, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Iacovelli
authors.affiliation: Department of Medical Oncology, AOU Ospedali Riuniti - Polytechnic University of the Marche Region, Ancona, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Burattini
authors.affiliation: Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.affiliation: Pathological Anatomy, Polytechnic University of the Marche Region School of Medicine United Hospitals, Ancona, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.affiliation: Department of Medical Oncology, AOU Ospedali Riuniti - Polytechnic University of the Marche Region, Ancona, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.affiliation: Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche Region, Ancona, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Principato
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D019295:Computational Biology; D004252:DNA Mutational Analysis / Q000379:methods*; D004268:DNA-Binding Proteins; D030541:Databases, Genetic; D020022:Genetic Predisposition to Disease; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
chemical_list: C400134:BAP1 protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C102195:PBRM1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D011495:Histone-Lysine N-Methyltransferase; C521636:SETD2 protein, human; D043222:Ubiquitin Thiolesterase
keywords: RCC; computational; mutations; polymorphisms; predictions