title: A Novel Approach to Evaluating Cancer Driver Gene Mutation Densities: Cytoskeleton-related Gene Candidates.
abstract: BACKGROUND
  Oncoprotein genes are over-represented in statically defined, low mutation-frequency fractions of cancer genome atlas (TCGA) datasets, consistent with a higher driver mutation density.
  
  
  METHODS
  We developed a "continuously variable fraction" (CVF) approach to defining high and low mutation-frequency groups.
  
  
  CONCLUSIONS
  Using the CVF approach, an oncoprotein set was shown to be associated with a TCGA, low mutation-frequency group in nine distinct cancer types, versus six, for statically defined sets; and a tumor-suppressor set was over-represented in the low mutation-frequency group in seven cancer types, notably including BRCA. The CVF approach identified single-mutation driver candidates, such as BRAF V600E in the thyroid cancer dataset. The CVF approach allowed investigation of cytoskeletal protein-related coding regions (CPCRs), leading to the conclusion that mutation of CPCRs occurs at a statistically significant, higher density in low mutation-frequency groups. Supporting online material for this article can be found at www.universityseminarassociates.com/Supporting_online_material_for_scholarly_pubs.php.
authors.affiliation: Department of Chemical and Biomedical Engineering, College of Engineering, Research Computing, University of South Florida, Tampa, FL, U.S.A.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Fawcett
authors.affiliation: Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, U.S.A.
authors.forename: Michele L
authors.initials: ML
authors.lastname: Parry
authors.affiliation: Immunology Program, Moffitt Cancer Center and Research Institute, Tampa, FL, U.S.A. gblanck@health.usf.edu.
authors.forename: George
authors.initials: G
authors.lastname: Blanck
mesh_terms: D000465:Algorithms; D019295:Computational Biology; D003599:Cytoskeleton / Q000378:metabolism*; D004252:DNA Mutational Analysis / Q000379:methods*; D030541:Databases, Genetic; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D016678:Genome; D015894:Genome, Human; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: TCGA; cytoskeletal proteins; mutation density; mutation frequency; oncoproteins; tumor suppressor proteins