Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate

Akhilesh Pandey (), Eric W. Stawiski (), Steffen Durinck, Harsha Gowda, Leonard D. Goldstein, Mustafa A. Barbhuiya, Markus S. Schröder, Sreelakshmi K. Sreenivasamurthy, Sun-Whe Kim, Sameer Phalke, Kushal Suryamohan, Kayla Lee, Papia Chakraborty, Vasumathi Kode, Xiaoshan Shi, Aditi Chatterjee, Keshava Datta, Aafaque A. Khan, Tejaswini Subbannayya, Jing Wang, Subhra Chaudhuri, Sanjiv Gupta, Braj Raj Shrivastav, Bijay S. Jaiswal, Satish S. Poojary, Shushruta Bhunia, Patricia Garcia, Carolina Bizama, Lorena Rosa, Wooil Kwon, Hongbeom Kim, Youngmin Han, Thakur Deen Yadav, Vedam L. Ramprasad, Amitabha Chaudhuri, Zora Modrusan, Juan Carlos Roa, Pramod Kumar Tiwari, Jin-Young Jang () and Somasekar Seshagiri ()
Additional contact information
Akhilesh Pandey: Institute of Bioinformatics
Eric W. Stawiski: Bioinformatics and Computational Biology Department, Genentech Inc
Steffen Durinck: Bioinformatics and Computational Biology Department, Genentech Inc
Harsha Gowda: Institute of Bioinformatics
Leonard D. Goldstein: Bioinformatics and Computational Biology Department, Genentech Inc
Mustafa A. Barbhuiya: Institute of Bioinformatics
Markus S. Schröder: Genentech Inc.
Sreelakshmi K. Sreenivasamurthy: Institute of Bioinformatics
Sun-Whe Kim: Division of Hepatobiliary and Pancreatic Surgery, Seoul National University Hospital, Seoul National University College of Medicine
Sameer Phalke: MedGenome Labs Pvt. Ltd.
Kushal Suryamohan: Research and Development Department, MedGenome Inc
Kayla Lee: Research and Development Department, MedGenome Inc
Papia Chakraborty: Research and Development Department, MedGenome Inc
Vasumathi Kode: Research and Development Department, MedGenome Inc
Xiaoshan Shi: Research and Development Department, MedGenome Inc
Aditi Chatterjee: Institute of Bioinformatics
Keshava Datta: Institute of Bioinformatics
Aafaque A. Khan: Institute of Bioinformatics
Tejaswini Subbannayya: Institute of Bioinformatics
Jing Wang: Research and Development Department, MedGenome Inc
Subhra Chaudhuri: Genentech Inc.
Sanjiv Gupta: Cancer Hospital and Research Institute
Braj Raj Shrivastav: Cancer Hospital and Research Institute
Bijay S. Jaiswal: Genentech Inc.
Satish S. Poojary: Jiwaji University
Shushruta Bhunia: Jiwaji University
Patricia Garcia: Millennium Institute on Immunology and Immunotherapy, School of Medicine, Pontificia Universidad Católica de Chile
Carolina Bizama: Millennium Institute on Immunology and Immunotherapy, School of Medicine, Pontificia Universidad Católica de Chile
Lorena Rosa: Applied Molecular and Cellular Biology PhD Program Universidad De la Frontera
Wooil Kwon: Division of Hepatobiliary and Pancreatic Surgery, Seoul National University Hospital, Seoul National University College of Medicine
Hongbeom Kim: Division of Hepatobiliary and Pancreatic Surgery, Seoul National University Hospital, Seoul National University College of Medicine
Youngmin Han: Division of Hepatobiliary and Pancreatic Surgery, Seoul National University Hospital, Seoul National University College of Medicine
Thakur Deen Yadav: Postgraduate Institute of Medical Education and Research
Vedam L. Ramprasad: MedGenome Labs Pvt. Ltd.
Amitabha Chaudhuri: Research and Development Department, MedGenome Inc
Zora Modrusan: Genentech Inc.
Juan Carlos Roa: Millennium Institute on Immunology and Immunotherapy, School of Medicine, Pontificia Universidad Católica de Chile
Pramod Kumar Tiwari: Jiwaji University
Jin-Young Jang: Division of Hepatobiliary and Pancreatic Surgery, Seoul National University Hospital, Seoul National University College of Medicine
Somasekar Seshagiri: Genentech Inc.

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Gallbladder 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.

Date: 2020
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DOI: 10.1038/s41467-020-17880-4

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