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 WangSubhra 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, Somasekar Seshagiri

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish (US)
Article number4225
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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