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Int. J. Mol. Sci. 2016, 17(5), 739; doi:10.3390/ijms17050739

A Tumor-Specific Neo-Antigen Caused by a Frameshift Mutation in BAP1 Is a Potential Personalized Biomarker in Malignant Peritoneal Mesothelioma

1
Institute of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China
2
Department of Obstetrics and Gynecology, Yuyao People’s Hospital, 800 Chengdong Road, Yuyao 315400, China
*
Authors to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 22 March 2016 / Revised: 28 April 2016 / Accepted: 4 May 2016 / Published: 14 May 2016
(This article belongs to the Special Issue Precision Medicine—From Bench to Bedside)
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Abstract

Malignant peritoneal mesothelioma (MPM) is an aggressive rare malignancy associated with asbestos exposure. A better understanding of the molecular pathogenesis of MPM will help develop a targeted therapy strategy. Oncogene targeted depth sequencing was performed on a tumor sample and paired peripheral blood DNA from a patient with malignant mesothelioma of the peritoneum. Four somatic base-substitutions in NOTCH2, NSD1, PDE4DIP, and ATP10B and 1 insert frameshift mutation in BAP1 were validated by the Sanger method at the transcriptional level. A 13-amino acids neo-peptide of the truncated Bap1 protein, which was produced as a result of this novel frameshift mutation, was predicted to be presented by this patient’s HLA-B protein. The polyclonal antibody of the synthesized 13-mer neo-peptide was produced in rabbits. Western blotting results showed a good antibody-neoantigen specificity, and Immunohistochemistry (IHC) staining with the antibody of the neo-peptide clearly differentiated neoplastic cells from normal cells. A search of the Catalogue of Somatic Mutations in Cancer (COSMIC) database also revealed that 53.2% of mutations in BAP1 were frameshift indels with neo-peptide formation. An identified tumor-specific neo-antigen could be the potential molecular biomarker for personalized diagnosis to precisely subtype rare malignancies such as MPM. View Full-Text
Keywords: neo-antigen; BAP1; personalized immunotherapy target; mesothelioma neo-antigen; BAP1; personalized immunotherapy target; mesothelioma
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Lai, J.; Zhou, Z.; Tang, X.-J.; Gao, Z.-B.; Zhou, J.; Chen, S.-Q. A Tumor-Specific Neo-Antigen Caused by a Frameshift Mutation in BAP1 Is a Potential Personalized Biomarker in Malignant Peritoneal Mesothelioma. Int. J. Mol. Sci. 2016, 17, 739.

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