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 Wang; Subhra 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

doi:10.1038/s41467-020-17880-4

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 Wang

Subhra 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

Institute of Bioinformatics
Manipal Academy of Higher Education
Mayo Clinic Rochester, MN
Genentech, Inc
MedGenome Inc.
Queensland Institute of Medical Research
Pennsylvania State University
SciGenom Labs Pvt. Ltd.
Seoul National University
MedGenome Labs Pvt. Ltd.
Cancer Hospital and Research Institute
Jiwaji University
Pontificia Universidad Católica de Chile
Universidad de la Frontera
Postgraduate Institute of Medical Education and Research
Narayana Nethralaya

Research output: Contribution to journal › Article › peer-review

66 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 language	English
Article number	4225
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-17880-4
State	Published - 1 Dec 2020
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1038/s41467-020-17880-4

Cite this

Pandey, A., Stawiski, E. W., Durinck, S., Gowda, H., Goldstein, L. D., Barbhuiya, M. A., Schröder, M. S., Sreenivasamurthy, S. K., Kim, S. W., Phalke, S., Suryamohan, K., Lee, K., Chakraborty, P., Kode, V., Shi, X., Chatterjee, A., Datta, K., Khan, A. A., Subbannayya, T., ... Seshagiri, S. (2020). Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate. Nature Communications, 11(1), Article 4225. https://doi.org/10.1038/s41467-020-17880-4

@article{9857e8bfeb274a49809cab25638b8b09,

title = "Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate",

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.",

author = "Akhilesh Pandey and Stawiski, \{Eric W.\} and Steffen Durinck and Harsha Gowda and Goldstein, \{Leonard D.\} and Barbhuiya, \{Mustafa A.\} and Schr{\"o}der, \{Markus S.\} and Sreenivasamurthy, \{Sreelakshmi K.\} and Kim, \{Sun Whe\} and Sameer Phalke and Kushal Suryamohan and Kayla Lee and Papia Chakraborty and Vasumathi Kode and Xiaoshan Shi and Aditi Chatterjee and Keshava Datta and Khan, \{Aafaque A.\} and Tejaswini Subbannayya and Jing Wang and Subhra Chaudhuri and Sanjiv Gupta and Shrivastav, \{Braj Raj\} and Jaiswal, \{Bijay S.\} and Poojary, \{Satish S.\} and Shushruta Bhunia and Patricia Garcia and Carolina Bizama and Lorena Rosa and Wooil Kwon and Hongbeom Kim and Youngmin Han and Yadav, \{Thakur Deen\} and Ramprasad, \{Vedam L.\} and Amitabha Chaudhuri and Zora Modrusan and Roa, \{Juan Carlos\} and Tiwari, \{Pramod Kumar\} and Jang, \{Jin Young\} and Somasekar Seshagiri",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41467-020-17880-4",

language = "English",

volume = "11",

journal = "Nature Communications",

issn = "2041-1723",

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Pandey, A, Stawiski, EW, Durinck, S, Gowda, H, Goldstein, LD, Barbhuiya, MA, Schröder, MS, Sreenivasamurthy, SK, Kim, SW, Phalke, S, Suryamohan, K, Lee, K, Chakraborty, P, Kode, V, Shi, X, Chatterjee, A, Datta, K, Khan, AA, Subbannayya, T, Wang, J, Chaudhuri, S, Gupta, S, Shrivastav, BR, Jaiswal, BS, Poojary, SS, Bhunia, S, Garcia, P, Bizama, C, Rosa, L, Kwon, W, Kim, H, Han, Y, Yadav, TD, Ramprasad, VL, Chaudhuri, A, Modrusan, Z, Roa, JC, Tiwari, PK, Jang, JY & Seshagiri, S 2020, 'Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate', Nature Communications, vol. 11, no. 1, 4225. https://doi.org/10.1038/s41467-020-17880-4

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

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.

UR - https://www.scopus.com/pages/publications/85089773219

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 -

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

Abstract

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