Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate
Akhilesh Pandey, Eric Stawiski, Steffen Durinck, Harsha Gowda, Leonard D. Goldstein, Mustafa A. Barbhuiya, Markus Schröder, Sreelakshmi K. Sreenivasamurthy, Sun‐Whe Kim, Sameer Phalke, Kushal Suryamohan, Kayla Lee, Papia Chakraborty, Vasumathi Kode, Xiaoshan Shi, Aditi Chatterjee, Keshava K. Datta, Aafaque Ahmad Khan, Tejaswini Subbannayya, Jing Wang, Subhra Chaudhuri, Sanjiv Gupta, Braj Raj Shrivastav, Bijay S. Jaiswal, Satish S. Poojary, Shushruta Bhunia, Patricia García, Carolina Bizama, Lorena Rosa, Wooil Kwon, Hongbeom Kim, Youngmin Han, Thakur Deen Yadav, Vedam L. Ramprasad, Amitabha Chaudhuri, Zora Modrušan, Juan Carlos Roa, Pramod Kumar Tiwari, Jin‐Young Jang, Somasekar Seshagiri
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.