Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate
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Published:2020-08-24
Issue:1
Volume:11
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Pandey AkhileshORCID, Stawiski Eric W., Durinck Steffen, Gowda Harsha, Goldstein Leonard D., Barbhuiya Mustafa A., Schröder Markus S., Sreenivasamurthy Sreelakshmi K.ORCID, Kim Sun-Whe, Phalke Sameer, Suryamohan Kushal, Lee Kayla, Chakraborty Papia, Kode Vasumathi, Shi Xiaoshan, Chatterjee AditiORCID, Datta Keshava, Khan Aafaque A., Subbannayya Tejaswini, Wang Jing, Chaudhuri Subhra, Gupta Sanjiv, Shrivastav Braj Raj, Jaiswal Bijay S., Poojary Satish S., Bhunia Shushruta, Garcia Patricia, Bizama Carolina, Rosa Lorena, Kwon Wooil, Kim HongbeomORCID, Han YoungminORCID, Yadav Thakur Deen, Ramprasad Vedam L., Chaudhuri Amitabha, Modrusan Zora, Roa Juan Carlos, Tiwari Pramod Kumar, Jang Jin-YoungORCID, Seshagiri SomasekarORCID
Abstract
AbstractGallbladder cancer (GBC) is an aggressive gastrointestinal malignancy with no approved targeted therapy. Here, we analyze exomes (n = 160), transcriptomes (n = 115), and low pass whole genomes (n = 146) from 167 gallbladder cancers (GBCs) from patients in Korea, India and Chile. In addition, we also sequence samples from 39 GBC high-risk patients and detect evidence of early cancer-related genomic lesions. Among the several significantly mutated genes not previously linked to GBC are ETS domain genes ELF3 and EHF, CTNNB1, APC, NSD1, KAT8, STK11 and NFE2L2. A majority of ELF3 alterations are frame-shift mutations that result in several cancer-specific neoantigens that activate T-cells indicating that they are cancer vaccine candidates. In addition, we identify recurrent alterations in KEAP1/NFE2L2 and WNT pathway in GBC. Taken together, these define multiple targetable therapeutic interventions opportunities for GBC treatment and management.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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