Comprehensive molecular characterization of gastric adenocarcinoma

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies

ICAR: endoscopic skull‐base surgery

n/

The Influence of Manga on the Graphic Novel

This material has been published in The Cambridge History of the Graphic Novel edited by Jan Baetens, Hugo Frey, Stephen E. Tabachnick. This version is free to view and download for personal use only. Not for re-distribution, re-sale or use in derivative works. © Cambridge University PressProviding a range of cogent examples, this chapter describes the influences of the Manga genre of comics strip on the Graphic Novel genre, over the last 35 years, considering the functions of domestication, foreignisation and transmedia on readers, markets and forms

Second primary malignancies in multiple myeloma: A review.

As survival times of multiple myeloma (MM) patients continue to improve, second primary malignancies (SPM) have become an increasingly relevant long-term risk among MM survivors. Population studies since the 1950s have consistently observed an increased incidence of hematologic SPMs, specifically acute leukemia, among MM survivors. Prolonged treatment with alkylators, especially melphalan, was associated with an increased hematologic SPM risk; likewise, autologous stem cell transplantation appeared to minimally increase SPM risk. Immunomodulatory drugs, specifically lenalidomide, was associated with an increased SPM incidence, although most studies concluded that the benefits of therapy outweighed any risks of SPM. Newer anti-myeloma therapy such as proteasome inhibitors and monoclonal antibodies did not appear to increase SPM risk although robust long-term follow-up is lacking. This review discusses current understanding regarding SPMs among survivors of MM, how different host-, disease- and treatment-related factors contribute to SPM incidence and highlights emerging screening guidelines and prognosis for SPMs

Integration and verification testing of the LSST camera

International audienceThe Integration and Verification Testing of the Large Synoptic Survey Telescope (LSST) Camera is described. The LSST Camera will be the largest astronomical camera ever constructed, featuring a 3.2 giga-pixel focal plane mosaic of 189 CCDs with in-vacuum controllers and readout, dedicated guider and wavefront CCDs, a three element corrector with a 1.6-meter diameter initial optic, six optical filters covering wavelengths from 320 to 1000 nm with a novel filter exchange mechanism, and camera-control and data acquisition capable of digitizing each image in two seconds. In this paper, we describe the integration processes under way to assemble the Camera and the associated verification testing program. The Camera assembly proceeds along two parallel paths: one for the focal plane and cryostat and the other for the Camera structure itself. A range of verification tests will be performed interspersed with assembly to verify design requirements with a test-as-you-build methodology. Ultimately, the cryostat will be installed into the Camera structure as the two assembly paths merge, and a suite of final Camera system tests performed. The LSST Camera is scheduled for completion and delivery to the LSST observatory in 2020

Comprehensive molecular characterization of urothelial bladder carcinoma

Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment of the disease. As part of The Cancer Genome Atlas project, we report here an integrated analysis of 131 urothelial carcinomasto provide a comprehensive landscape of molecular alterations. There were statistically significant recurrent mutations in 32 genes, including multiple genes involved in cell-cycle regulation, chromatin regulation, and kinase signalling pathways, as well as 9 genes not previously reported as significantly mutated in any cancer. RNA sequencing revealed four expression subtypes, two of which (papillary-like and basal/squamous-like) were also evident in microRNA sequencing and protein data. Whole-genome and RNA sequencing identified recurrent in-frame activating FGFR3-TACC3 fusions and expression or integration of several viruses (including HPV16) that are associated with gene inactivation. Our analyses identified potential therapeutic targets in 69% of the tumours, including 42% with targets in the phosphatidylinositol-3-OH kinase/AKT/mTOR pathway and 45% with targets (including ERBB2) in the RTK/MAPK pathway. Chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far, indicating the future possibility of targeted therapy for chromatin abnormalitiesclose27