RESUMO
Annotation of prostate cancer genomes provides a foundation for discoveries that can impact disease understanding and treatment. Concordant assessment of DNA copy number, mRNA expression, and focused exon resequencing in 218 prostate cancer tumors identified the nuclear receptor coactivator NCOA2 as an oncogene in approximately 11% of tumors. Additionally, the androgen-driven TMPRSS2-ERG fusion was associated with a previously unrecognized, prostate-specific deletion at chromosome 3p14 that implicates FOXP1, RYBP, and SHQ1 as potential cooperative tumor suppressors. DNA copy-number data from primary tumors revealed that copy-number alterations robustly define clusters of low- and high-risk disease beyond that achieved by Gleason score. The genomic and clinical outcome data from these patients are now made available as a public resource.
Assuntos
Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Genoma Humano , Proteínas de Fusão Oncogênica/genética , Neoplasias da Próstata/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Cromossomos Humanos Par 3/genética , Hibridização Genômica Comparativa , Dosagem de Genes , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias da Próstata/patologia , Transdução de Sinais , Transplante Heterólogo , Células Tumorais CultivadasRESUMO
Activation of the Fanconi anemia (FA) DNA damage-response pathway results in the monoubiquitination of FANCD2, which is regulated by the nuclear FA core ubiquitin ligase complex. A FANCD2 protein sequence-based homology search facilitated the discovery of FANCI, a second monoubiquitinated component of the FA pathway. Biallelic mutations in the gene coding for this protein were found in cells from four FA patients, including an FA-I reference cell line.
Assuntos
Reparo do DNA/genética , Proteínas de Grupos de Complementação da Anemia de Fanconi/genética , Proteínas de Grupos de Complementação da Anemia de Fanconi/metabolismo , Anemia de Fanconi/genética , Sequência de Aminoácidos , Sequência de Bases , Western Blotting , Biologia Computacional , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo , Células HeLa , Humanos , Imunoprecipitação , Microscopia de Fluorescência , Dados de Sequência Molecular , Mutação/genética , Análise de Sequência de DNA , UbiquitinaçãoRESUMO
Subjects who withdraw from diet clinical trials are a drain on limited resources and reduce statistical power. Dropout pattern data, collected during a clinical trial for which the primary findings compared weight loss from three dieting protocols, are examined using survival analysis and found to be exponentially distributed. The predicted probability of remaining in the study is 83% for 30 days and 60% for 84 days. Survival analysis methods consider subjects who did not return after the initial visit and others who may have continued dieting beyond study termination. When applied to clinical trials, this type of analysis provides valuable information for planning and budgeting of future trials. Inclusion of a 1- to 2-week run-in period at the beginning of the study may improve retention. Otherwise, the diet researcher should consider increasing initial randomized sample size by approximately 10% to 25% as an allowance for early withdrawals.
