title: Stratifying melanoma and breast cancer TCGA datasets on the basis of the CNV of transcription factor binding sites common to proliferation- and apoptosis-effector genes.
abstract: Transcription factors that activate both proliferation- and apoptosis-effector genes, along with a number of related observations, have led to a proposal for a feed forward mechanism of activating the two gene classes, whereby a certain concentration of a transcription factor activates the proliferation-effector genes and a higher concentration of the transcription factor activates the apoptosis-effector genes. We reasoned that this paradigm of regulation could lead to, in the cancer setting, a selection for relatively reduced copy numbers of apoptosis-effector gene, transcription factor binding sites (TFBS). Thus, the aim of this investigation was to examine the DNA sequencing read depths of TFBS for a set of proliferation- and apoptosis-effector genes, normalized to the read depths found in matching blood samples, as provided by the cancer genome atlas (TCGA); and thereby document copy number differences among these TFBS. We determined that the melanoma and breast cancer, TCGA datasets could be divided into three categories: (i) no detectable copy number variation for the proliferation- and apoptosis-effector, shared TFBS; (ii) a relative increase in the copy number of proliferation-effector gene TFBS, compared with the copy number of the apoptosis-effector gene TFBS; and (iii) a relative decrease in the number of proliferation-effector gene TFBS. Thus, we conclude that changes in the relative copies of the shared TFBS, for proliferation- and apoptosis-effector genes, have the potential of impacting tumor cell proliferative and apoptotic capacities.
authors.affiliation: Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, United States.
authors.forename: James A
authors.initials: JA
authors.lastname: Mauro
authors.affiliation: Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, United States.
authors.forename: John M
authors.initials: JM
authors.lastname: Yavorski
authors.affiliation: Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, United States; Immunology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States. Electronic address: gblanck@health.usf.edu.
authors.forename: George
authors.initials: G
authors.lastname: Blanck
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D056915:DNA Copy Number Variations; D030541:Databases, Genetic / Q000145:classification; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014157:Transcription Factors
keywords: Apoptosis-effector genes; Cancer; Copy number variation; Feed-forward mechanism; Proliferation-effector genes; Transcription factor binding sites