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

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

Observation of Hadronic W Decays in t-tbar Events with the Collider Detector at Fermilab

We observe hadronic W decays in t-tbar -> W (-> l nu) + >= 4 jet events using a 109 pb-1 data sample of p-pbar collisions at sqrt{s} = 1.8 TeV collected with the Collider Detector at Fermilab (CDF). A peak in the dijet invariant mass distribution is obtained that is consistent with W decay and inconsistent with the background prediction by 3.3 standard deviations. From this peak we measure the W mass to be 77.2 +- 4.6 (stat+syst) GeV/c^2. This result demonstrates the presence of two W bosons in t-tbar candidates in the W (-> l nu) + >= 4 jet channel.Comment: 20 pages, 4 figures, submitted to PR

Measurement of Dijet Angular Distributions at CDF

We have used 106 pb^-1 of data collected in proton-antiproton collisions at sqrt(s)=1.8 TeV by the Collider Detector at Fermilab to measure jet angular distributions in events with two jets in the final state. The angular distributions agree with next to leading order (NLO) predictions of Quantum Chromodynamics (QCD) in all dijet invariant mass regions. The data exclude at 95% confidence level (CL) a model of quark substructure in which only up and down quarks are composite and the contact interaction scale is Lambda_ud(+) < 1.6 TeV or Lambda_ud(-) < 1.4 TeV. For a model in which all quarks are composite the excluded regions are Lambda(+) < 1.8 TeV and Lambda(-) < 1. 6 TeV.Comment: 16 pages, 2 figures, 2 tables, LaTex, using epsf.sty. Submitted to Physical Review Letters on September 17, 1996. Postscript file of full paper available at http://www-cdf.fnal.gov/physics/pub96/cdf3773_dijet_angle_prl.p

Search for charged Higgs decays of the top quark using hadronic tau decays

We present the result of a search for charged Higgs decays of the top quark, produced in $p\bar{p}$ collisions at $\surd s =$ 1.8 TeV. When the charged Higgs is heavy and decays to a tau lepton, which subsequently decays hadronically, the resulting events have a unique signature: large missing transverse energy and the low-charged-multiplicity tau. Data collected in the period 1992-1993 at the Collider Detector at Fermilab, corresponding to 18.7$\pm$0.7~pb$^{-1}$, exclude new regions of combined top quark and charged Higgs mass, in extensions to the standard model with two Higgs doublets.Comment: uuencoded, gzipped tar file of LaTeX and 6 Postscript figures; 11 pp; submitted to Phys. Rev.

Inclusive jet cross section in pˉp{\bar p p} collisions at s=1.8\sqrt{s}=1.8 TeV

The inclusive jet differential cross section has been measured for jet transverse energies, $E_T$, from 15 to 440 GeV, in the pseudorapidity region 0.1$\leq | \eta| \leq$0.7. The results are based on 19.5 pb$^{-1}$ of data collected by the CDF collaboration at the Fermilab Tevatron collider. The data are compared with QCD predictions for various sets of parton distribution functions. The cross section for jets with $E_T>200$ GeV is significantly higher than current predictions based on O($\alpha_s^3$) perturbative QCD calculations. Various possible explanations for the high-$E_T$ excess are discussed.Comment: 8 pages with 2 eps uu-encoded figures Submitted to Physical Review Letter

Measurement of the Associated γ+μ±\gamma + \mu^\pm Production Cross Section in ppˉp \bar p Collisions at s=1.8\sqrt{s} = 1.8 TeV

We present the first measurement of associated direct photon + muon production in hadronic collisions, from a sample of 1.8 TeV $p \bar p$ collisions recorded with the Collider Detector at Fermilab. Quantum chromodynamics (QCD) predicts that these events are primarily from the Compton scattering process $cg \to c\gamma$, with the final state charm quark producing a muon. Hence this measurement is sensitive to the charm quark content of the proton. The measured cross section of $29\pm 9 pb^{-1}$ is compared to a leading-order QCD parton shower model as well as a next-to-leading-order QCD calculation.Comment: 12 pages, 4 figures Added more detailed description of muon background estimat

Repeated cycles of Clostridium-directed enzyme prodrug therapy result in sustained antitumour effects in vivo

The unique properties of the tumour microenvironment can be exploited by using recombinant anaerobic clostridial spores as highly selective gene delivery vectors. Although several recombinant Clostridium species have been generated during the past decade, their efficacy has been limited. Our goal was to substantially improve the prospects of clostridia as a gene delivery vector. Therefore, we have assessed a series of nitroreductase (NTR) enzymes for their capacity to convert the innocuous CB1954 prodrug to its toxic derivative. Among the enzymes tested, one showed superior prodrug turnover characteristics. In addition, we established an efficient gene transfer procedure, based on conjugation, which allows for the first time genetic engineering of Clostridium strains with superior tumour colonisation properties with high success rates. This conjugation procedure was subsequently used to create a recombinant C. sporogenes overexpressing the isolated NTR enzyme. Finally, analogous to a clinical setting situation, we have tested the effect of multiple consecutive treatment cycles, with antibiotic bacterial clearance between cycles. Importantly, this regimen demonstrated that intravenously administered spores of NTR-recombinant C. sporogenes produced significant antitumour efficacy when combined with prodrug administration

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN