204 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

    Measurements of differential production cross sections for a Z boson in association with jets in pp collisions at root s=8 TeV

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    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

    Search for leptophobic Z ' bosons decaying into four-lepton final states in proton-proton collisions at root s=8 TeV

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    Search for black holes and other new phenomena in high-multiplicity final states in proton-proton collisions at root s=13 TeV

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    Search for heavy resonances decaying into a vector boson and a Higgs boson in final states with charged leptons, neutrinos, and b quarks

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    Search for high-mass diphoton resonances in proton-proton collisions at 13 TeV and combination with 8 TeV search

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    Measurement of the azimuthal anisotropy of Y(1S) and Y(2S) mesons in PbPb collisions at √S^{S}NN = 5.02 TeV

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    The second-order Fourier coefficients (υ2_{2}) characterizing the azimuthal distributions of ΄(1S) and ΄(2S) mesons produced in PbPb collisions at sNN\sqrt{s_{NN}} = 5.02 TeV are studied. The ΄mesons are reconstructed in their dimuon decay channel, as measured by the CMS detector. The collected data set corresponds to an integrated luminosity of 1.7 nb−1^{-1}. The scalar product method is used to extract the υ2_{2} coefficients of the azimuthal distributions. Results are reported for the rapidity range |y| < 2.4, in the transverse momentum interval 0 < pT_{T} < 50 GeV/c, and in three centrality ranges of 10–30%, 30–50% and 50–90%. In contrast to the J/ψ mesons, the measured υ2_{2} values for the ΄ mesons are found to be consistent with zero

    The Integrated Genomic Landscape of Thymic Epithelial Tumors

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    Thymic epithelial tumors (TETs) are one of the rarest adult malignancies. Among TETs, thymoma is the most predominant, characterized by a unique association with autoimmune diseases, followed by thymic carcinoma, which is less common but more clinically aggressive. Using multi-platform omics analyses on 117 TETs, we define four subtypes of these tumors defined by genomic hallmarks and an association with survival and World Health Organization histological subtype. We further demonstrate a marked prevalence of a thymoma-specific mutated oncogene, GTF2I, and explore its biological effects on multi-platform analysis. We further observe enrichment of mutations in HRAS, NRAS, and TP53. Last, we identify a molecular link between thymoma and the autoimmune disease myasthenia gravis, characterized by tumoral overexpression of muscle autoantigens, and increased aneuploidy. Radovich et al. perform multi-platform analyses of thymic epithelial tumors. They identify high prevalence of GTF2I mutations and enrichment of mutations in HRAS, NRAS, and TP53 and link overexpression of muscle autoantigens and increased aneuploidy in thymoma and patients’ risk of having myasthenia gravis
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