108 research outputs found

    An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

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    For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

    Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

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    Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

    AlteraçÔes nas reservas de sementes de Dalbergia nigra ((Vell.) Fr. All. ex Benth.) durante a hidratação

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    Seed imbibitions is the first stage of the germination process and is characterized by the hydration of tissues and cells and the activation and/or induction of the enzymes responsible for mobilizing reserves for respiration and the construction of new cell structures. The objective of this study was to investigate the alterations in reserve substances during slow hydration of Bahia Rosewood (Dalbergia nigra) seeds in water. Seeds from two different lots (Lot I and II) were placed in saturated desiccators (95-99% RH) to hydrate at 15 and 25 °C until water contents of 10, 15, 20 and 25% were reached. At each level of hydration, changes in lipid reserves, soluble carbohydrates, starch and soluble proteins were evaluated. The mobilization of reserves was similarly assessed in both lots, with no differences being observed between the two hydration temperatures. Lipid contents showed little variation during hydration, while the contents of soluble carbohydrates and starch decreased after the 15% water content level. Soluble proteins showed a gradual tendency to decrease between the control (dry seeds) up to 25% water content
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