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 - Funding Information:
The authors would like to acknowledge Genentech NGS lab and Bioinformatics groups for their help with the project. We also thank Dr. Ruchi Chaudhary, MedGenome, for bioinformatics support. A.P. was supported by NIH Grant R01CA184165 and NCI’s Clinical Proteomic Tumor Analysis Consortium Initiative U24CA210985. P.K.T was supported by grants from DST-SERB, Govt. of India.
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 -