title: Comparison of gene expression patterns across 12 tumor types identifies a cancer supercluster characterized by TP53 mutations and cell cycle defects.
abstract: Transcriptional profile-based subtypes of cancer are often viewed as identifying different diseases from the same tissue origin. Understanding the mechanisms driving the subtypes may be key in development of novel therapeutics but is challenged by lineage-specific expression signals. Using a t-test statistics approach, we compared gene expression subtypes across 12 tumor types, which identified eight transcriptional superclusters characterized by commonly activated disease pathways and similarities in gene expression. One of the largest superclusters was determined by the upregulation of a proliferation signature, significant enrichment in TP53 mutations, genomic loss of CDKN2A (p16(ARF)), evidence of increased numbers of DNA double strand breaks and high expression of cyclin B1 protein. These correlations suggested that abrogation of the P53-mediated apoptosis response to DNA damage results in activation of cell cycle pathways and represents a common theme in cancer. A second consistent pattern, observed in 9 of 11 solid tumor types, was a subtype related to an activated tumor-associated stroma. The similarity in transcriptional footprints across cancers suggested that tumor subtypes are commonly unified by a limited number of molecular themes.
authors.affiliation: 1] Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] Catedra de Bioinformatica, Tecnologico de Monterrey, Monterrey, Nuevo Leon, Mexico.
authors.forename: E
authors.initials: E
authors.lastname: Martínez
authors.affiliation: 1] Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Niigata, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yoshihara
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Mills
authors.affiliation: Catedra de Bioinformatica, Tecnologico de Monterrey, Monterrey, Nuevo Leon, Mexico.
authors.forename: V
authors.initials: V
authors.lastname: Treviño
authors.affiliation: 1] Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: R G W
authors.initials: RG
authors.lastname: Verhaak
mesh_terms: D002453:Cell Cycle / Q000235:genetics*; D056744:Cyclin B1 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D015870:Gene Expression / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D056744:Cyclin B1; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016159:Tumor Suppressor Protein p53
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