Comprehensive Genomic Characterization of Upper Tract Urothelial Carcinoma
EUROPEAN UROLOGY
Authors: Moss, Tyler J.; Qi, Yuan; Xi, Liu; Peng, Bo; Kim, Tae-Beom; Ezzedine, Nader E.; Mosqueda, Maribel E.; Guo, Charles C.; Czerniak, Bogdan A.; Ittmann, Michael; Wheeler, David A.; Lerner, Seth P.; Matin, Surena F.
Abstract
Background: Upper urinary tract urothelial cancer (UTUC) may have unique etiologic and genomic factors compared to bladder cancer. Objective: To characterize the genomic landscape of UTUC and provide insights into its biology using comprehensive integrated genomic analyses. Design, setting, and participants: We collected 31 untreated snap-frozen UTUC samples from two institutions and carried out whole-exome sequencing (WES) of DNA, RNA sequencing (RNAseq), and protein analysis. Outcome measurements and statistical analysis: Adjusting for batch effects, consensus mutation calls from independent pipelines identified DNA mutations, gene expression clusters using unsupervised consensus hierarchical clustering (UCHC), and protein expression levels that were correlated with relevant clinical variables, The Cancer Genome Atlas, and other published data. Results and limitations: WES identified mutations in FGFR3 (74.1%; 92% low-grade, 60% high-grade), KMT2D (44.4%), PIK3CA (25.9%), and TP53 (22.2%). APOBEC and CpG were the most common mutational signatures. UCHC of RNAseq data segregated samples into four molecular subtypes with the following characteristics. Cluster 1: no PIK3CA mutations, nonsmokers, high-grade
Studying protein isoforms of the adaptor SETA/CIN85/Ruk with monoclonal antibodies
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Authors: Finniss, S; Movsisyan, A; Billecke, C; Schmidt, M; Randazzo, L; Chen, BH; Bogler, O
Abstract
SETA/CIN85/Ruk is a multifunctional adaptor protein involved in signal transduction and attenuation downstream of receptor tyrosine kinases. It has a modular structure, and various isoforms that combine different protein-protein interaction domains have been proposed based on cDNA analysis. As a first step towards understanding SETA/CIN85/Ruk isoforms at the protein level, we have characterized 5 monoclonal antibodies against this protein. Three of these were used to study lysates fractionated on a pH gradient, leading to the identification of various SETA/CIN85/Ruk proteins on the basis of pI and apparent molecular weight. While good correspondence with proteins predicted from cDNA analysis was found for two isoforms, in most cases it was not possible to make an unequivocal assignment. We conclude that additional splice variants remain to be described, and that a deeper understanding of SETA/CIN85/Ruk post-translational processing and modification is necessary to gain further understanding of this complex gene product. (C) 2004 Elsevier Inc. All rights reserved.
COA
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