nad a22 4500 569304822 20190726062910.0 cr unu---uuuuu 190726e20190611xx s 000 0 eng 10.5167/uzh-171724 doi 10.1016/j.tranon.2019.05.005 doi (ZORA)oai:www.zora.uzh.ch:171724 (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/348928 610 ddc 31200327 pmid Allele Loss and Reduced Expression of CYCLOPS Genes is a Characteristic Feature of Chromophobe Renal Cell Carcinoma [Elektronische Daten] [Riuko Ohashi, Peter Schraml, Aashil Batavia, Silvia Angori, Patrik Simmler, Niels Rupp, Yoichi Ajioka, Esther Oliva, Holger Moch] openAccess eu-repo Copy-number alterations Yielding Cancer Liabilities Owing to Partial losS (CYCLOPS) genes have been recently identified as the most enriched class of copy-number associated gene dependencies in human cancer. These genes are cell essential and render tumor cells highly sensitive to the expression of the remaining copy. Chromophobe renal cell carcinoma (chRCC) is characterized by frequent chromosomal deletions, but the relevance of CYCLOPS genes in this tumor subtype is unclear. We found 39 (31%) of 124 recently published candidate CYCLOPS genes (B. Paolella et al., eLife 2017;6:e23268) located on 7 autosomes that are frequently lost in chRCC. GISTIC and RNA-seq data obtained from the TCGA-KICH database showed that 62% of these CYCLOPS genes had significantly lower expression levels in samples with deletion of the respective gene. As copy number (CN) loss of the CYCLOPS gene SF3B1 (Splicing factor 3B subunit 1) has been recently reported in 71% chRCC, we explored the relevance of SF3B1 CN alteration and SF3B1 expression in a set of chRCC and additional oncocytic renal neoplasms. The frequency of SF3B1 CN loss (65%) was similar to that obtained from the TCGA-KICH database and correlated significantly with both lower SF3B1 mRNA (P < .05) and protein expression (P < .001). Other tumor subtypes with oncocytic cytoplasm had normal SF3B1 CN and displayed strong SF3B1 protein expression. These results suggest that CN loss of CYCLOPS genes is a characteristic feature in chRCC. Since many CYCLOPS genes code for components of proteasomes and transcriptional regulation, their alteration could make chRCC vulnerable to targeted drugs. Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0 ethresearch Institute of Pathology and Molecular Pathology zora Ohashi Riuko joint author Schraml Peter joint author Batavia Aashil joint author Angori Silvia joint author Simmler Patrik joint author Rupp Niels joint author Ajioka Yoichi joint author Oliva Esther joint author Moch Holger joint author Translational Oncology 12(9):1131-1137 https://www.zora.uzh.ch/id/eprint/171724/1/Ohashi_transl.oncol._2019.pdf text/html WWW-Backlink auf das Repository 1 Journal Article PeerReviewed zora ZORA 856 40 https://www.zora.uzh.ch/id/eprint/171724/1/Ohashi_transl.oncol._2019.pdf text/html WWW-Backlink auf das Repository ZORA 700 1- Ohashi Riuko joint author ZORA 700 1- Schraml Peter joint author ZORA 700 1- Batavia Aashil joint author ZORA 700 1- Angori Silvia joint author ZORA 700 1- Simmler Patrik joint author ZORA 700 1- Rupp Niels joint author ZORA 700 1- Ajioka Yoichi joint author ZORA 700 1- Oliva Esther joint author ZORA 700 1- Moch Holger joint author ZORA 773 0- Translational Oncology 12(9):1131-1137 ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/348928 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Ohashi Riuko joint author ETHRESEARCH 700 1- Schraml Peter joint author ETHRESEARCH 700 1- Batavia Aashil joint author ETHRESEARCH 700 1- Angori Silvia joint author ETHRESEARCH 700 1- Simmler Patrik joint author ETHRESEARCH 700 1- Rupp Niels joint author ETHRESEARCH 700 1- Ajioka Yoichi joint author ETHRESEARCH 700 1- Oliva Esther joint author ETHRESEARCH 700 1- Moch Holger joint author ETHRESEARCH 773 0- Translational Oncology Amsterdam : Elsevier 12 (9), pp. 1131-1137 BK010053 XK010053 XK010000 ZORA ZORA ZORA Journal Article openAccess ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access