한빛사 논문
Akhilesh Pandey1,2,3,19,20,*, Eric W. Stawiski4,5,6,19,20*, Steffen Durinck4,5,19, Harsha Gowda1,7,19, Leonard D. Goldstein4,5, Mustafa A. Barbhuiya1,8, Markus S. Schröder5,9, Sreelakshmi K. Sreenivasamurthy1, Sun-Whe Kim10, Sameer Phalke11, Kushal Suryamohan6, Kayla Lee6, Papia Chakraborty6, Vasumathi Kode6, Xiaoshan Shi6, Aditi Chatterjee1, Keshava Datta1, Aafaque A. Khan1, Tejaswini Subbannayya1, Jing Wang6, Subhra Chaudhuri5, Sanjiv Gupta12, Braj Raj Shrivastav13, Bijay S. Jaiswal5, Satish S. Poojary14, Shushruta Bhunia14, Patricia Garcia15, Carolina Bizama15, Lorena Rosa16, Wooil Kwon10, Hongbeom Kim10, Youngmin Han10, Thakur Deen Yadav17, Vedam L. Ramprasad11, Amitabha Chaudhuri6, Zora Modrusan5, Juan Carlos Roa15, Pramod Kumar Tiwari14,20, Jin-Young Jang10,20,* & Somasekar Seshagiri5,18,20,*
1 Institute of Bioinformatics, Bangalore, Karnataka 560066, India. 2 Manipal Academy of Higher Education (MAHE), Manipal, Karnataka 576104, India. 3 Center for Individualized Medicine and Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA. 4 Bioinformatics and Computational Biology Department, Genentech Inc, South San Francisco, CA 94080, USA. 5 Molecular Biology Department, Genentech Inc., South San Francisco, CA 94080, USA. 6 Research and Development Department, MedGenome Inc, Foster City, CA 94404, USA. 7 QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia. 8 Department of Pathology and Laboratory Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. 9 SciGenom Labs, Cochin, Kerala 682037, India. 10 Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 08826, South Korea. 11 Research and Development Department, MedGenome Labs Pvt. Ltd., Bangalore, Karnataka 560099, India. 12 Department of Pathology, Cancer Hospital and Research Institute, Gwalior, Madhya Pradesh 474009, India. 13 Department of Surgical Oncology, Cancer Hospital and Research Institute, Gwalior, Madhya Pradesh 474009, India. 14 Jiwaji University, Gwalior, Madhya Pradesh 474011, India. 15 Department of Pathology, Millennium Institute on Immunology and Immunotherapy, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile. 16 Applied Molecular and Cellular Biology PhD Program Universidad De la Frontera, Temuco, Chile. 17 Department of Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. 18 SciGenom Research Foundation, 3rd Floor, Narayana Nethralaya Building, Narayana Health City, #258/A, Bommasandra, Hosur Road, Bangalore, Karnataka 560099, India.
19 These authors contributed equally: Akhilesh Pandey, Eric W. Stawiski, Steffen Durinck, Harsha Gowda.
20 These authors jointly supervised this work: Akhilesh Pandey, Eric W. Stawiski, Pramod Kumar Tiwari, Jin-Young Jang, Somasekar Seshagiri.
*Corresponding author
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.
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TOP52020년 후보
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