TY - JOUR
T1 - Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate
AU - Pandey, Akhilesh
AU - Stawiski, Eric W.
AU - Durinck, Steffen
AU - Gowda, Harsha
AU - Goldstein, Leonard D.
AU - Barbhuiya, Mustafa A.
AU - Schröder, Markus S.
AU - Sreenivasamurthy, Sreelakshmi K.
AU - Kim, Sun Whe
AU - Phalke, Sameer
AU - Suryamohan, Kushal
AU - Lee, Kayla
AU - Chakraborty, Papia
AU - Kode, Vasumathi
AU - Shi, Xiaoshan
AU - Chatterjee, Aditi
AU - Datta, Keshava
AU - Khan, Aafaque A.
AU - Subbannayya, Tejaswini
AU - Wang, Jing
AU - Chaudhuri, Subhra
AU - Gupta, Sanjiv
AU - Shrivastav, Braj Raj
AU - Jaiswal, Bijay S.
AU - Poojary, Satish S.
AU - Bhunia, Shushruta
AU - Garcia, Patricia
AU - Bizama, Carolina
AU - Rosa, Lorena
AU - Kwon, Wooil
AU - Kim, Hongbeom
AU - Han, Youngmin
AU - Yadav, Thakur Deen
AU - Ramprasad, Vedam L.
AU - Chaudhuri, Amitabha
AU - Modrusan, Zora
AU - Roa, Juan Carlos
AU - Tiwari, Pramod Kumar
AU - Jang, Jin Young
AU - Seshagiri, Somasekar
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-020-17880-4
DO - 10.1038/s41467-020-17880-4
M3 - Article
C2 - 32839463
AN - SCOPUS:85089773219
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4225
ER -