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

Author

Listed:
  • Akhilesh Pandey

    (Institute of Bioinformatics
    Manipal Academy of Higher Education (MAHE)
    Center for Individualized Medicine and Department of Laboratory Medicine and Pathology, Mayo Clinic)

  • Eric W. Stawiski

    (Bioinformatics and Computational Biology Department, Genentech Inc
    Genentech Inc.
    Research and Development Department, MedGenome Inc)

  • Steffen Durinck

    (Bioinformatics and Computational Biology Department, Genentech Inc
    Genentech Inc.)

  • Harsha Gowda

    (Institute of Bioinformatics
    QIMR Berghofer Medical Research Institute)

  • Leonard D. Goldstein

    (Bioinformatics and Computational Biology Department, Genentech Inc
    Genentech Inc.)

  • Mustafa A. Barbhuiya

    (Institute of Bioinformatics
    Pennsylvania State University College of Medicine)

  • Markus S. Schröder

    (Genentech Inc.
    SciGenom Labs)

  • 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.
    SciGenom Research Foundation, 3rd Floor, Narayana Nethralaya Building, Narayana Health City)

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.

Suggested Citation

  • 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 &, 2020. "Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17880-4
    DOI: 10.1038/s41467-020-17880-4
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