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

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

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

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Precise measurement of the Ds+D^+_s lifetime at Belle II

We measure the lifetime of the $D_s^+$ meson using a data sample of 207 fb$^{-1}$ collected by the Belle II experiment running at the SuperKEKB asymmetric-energy $e^+ e^-$ collider. The lifetime is determined by fitting the decay-time distribution of a sample of $116\times 10^3$ $D_s^+\rightarrow\phi\pi^+$ decays. Our result is \tau^{}_{D^+_s} = (498.7\pm 1.7\,^{+1.1}_{-0.8}) fs, where the first uncertainty is statistical and the second is systematic. This result is significantly more precise than previous measurements.Comment: 7 pages, 4 figures, to be submitted to Physical Review Letter

Tests of light-lepton universality in angular asymmetries of B0→D∗−ℓνB^0 \to D^{*-} \ell \nu decays

We present the first comprehensive tests of light-lepton universality in the angular distributions of semileptonic \Bz-meson decays to charged spin-1 charmed mesons. We measure five angular-asymmetry observables as functions of the decay recoil that are sensitive to lepton-universality-violating contributions. We use events where one neutral \B is fully reconstructed in \PUpsilonFourS{} \to\B\overline{B} decays in data corresponding to \lumion integrated luminosity from electron-positron collisions collected with the \belletwo detector. We find no significant deviation from the standard model expectations

First measurement of R(Xτ/ℓ)R(X_{\tau/\ell}) as an inclusive test of the b→cτνb \to c \tau \nu anomaly

We measure the tau-to-light-lepton ratio of inclusive $B$-meson branching fractions $R(X_{\tau/\ell}) \equiv \mathcal{B}(B\to X \tau \nu)/\mathcal{B}(B \to X \ell \nu)$, where $\ell$ indicates an electron or muon, and thereby test the universality of charged-current weak interactions. We select events that have one fully reconstructed $B$ meson and a charged lepton candidate from $189~\mathrm{fb}^{-1}$ of electron-positron collision data collected with the Belle II detector. We find $R(X_{\tau/\ell}) = 0.228 \pm 0.016~(\mathrm{stat}) \pm 0.036~(\mathrm{syst})$, in agreement with standard-model expectations. This is the first direct measurement of $R(X_{\tau/\ell})$

Measurement of branching fractions and direct CPCP asymmetries for B→KπB \to K\pi and B→ππB\to\pi\pi decays at Belle II

We report measurements of the branching fractions and direct $\it{CP}$ asymmetries of the decays $B^0 \to K^+ \pi^-$, $B^+ \to K^+ \pi^0$, $B^+ \to K^0 \pi^+$, and $B^0 \to K^0 \pi^0$, and use these for testing the standard model through an isospin-based sum rule. In addition, we measure the branching fraction and direct $\it{CP}$ asymmetry of the decay $B^+ \to \pi^+\pi^0$ and the branching fraction of the decay $B^0 \to \pi^+\pi^-$. The data are collected with the Belle II detector from $e^+e^-$ collisions at the $\Upsilon(4S)$ resonance produced by the SuperKEKB asymmetric-energy collider and contain $387\times 10^6$ bottom-antibottom meson pairs. Signal yields are determined in two-dimensional fits to background-discriminating variables, and range from 500 to 3900 decays, depending on the channel. We obtain $-0.03 \pm 0.13 \pm 0.04$ for the sum rule, in agreement with the standard model expectation of zero and with a precision comparable to the best existing determinations

Measurement of C ⁣PC\!P asymmetries and branching-fraction ratios for B±→DK±B^\pm \to DK^\pm and Dπ±D\pi^\pm with D→KS0K±π∓D\to K^0_{\rm S} K^\pm\pi^\mp using Belle and Belle II data

We measure $C\!P$ asymmetries and branching-fraction ratios for $B^\pm \to DK^\pm$ and $D\pi^\pm$ decays with $D\to K^0_{\rm S} K^\pm\pi^\mp$, where $D$ is a superposition of $D^0$ and $\bar{D}^0$. We use the full data set of the Belle experiment, containing $772\times 10^6~B\bar{B}$ pairs, and data from the Belle~II experiment, containing $387\times 10^6~B\bar{B}$ pairs, both collected in electron-positron collisions at the $\Upsilon(4S)$ resonance. Our results provide model-independent information on the unitarity triangle angle $\phi_3$.Comment: 26 pages, 8 figure