دورية أكاديمية
Neoantigenic Potential of Complex Chromosomal Rearrangements in Mesothelioma.
| العنوان: | Neoantigenic Potential of Complex Chromosomal Rearrangements in Mesothelioma. |
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| المؤلفون: | Mansfield AS; Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota., Peikert T; Division of Pulmonary Medicine and Critical Care, Mayo Clinic, Rochester, Minnesota., Smadbeck JB; Center for Individualized Medicine, Biomarker Discovery Group, Mayo Clinic, Rochester, Minnesota., Udell JBM; Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota., Garcia-Rivera E; nference, Cambridge, Massachusetts., Elsbernd L; Department of Immunology, Mayo Clinic, Rochester, Minnesota., Erskine CL; Department of Immunology, Mayo Clinic, Rochester, Minnesota., Van Keulen VP; Department of Immunology, Mayo Clinic, Rochester, Minnesota., Kosari F; Center for Individualized Medicine, Biomarker Discovery Group, Mayo Clinic, Rochester, Minnesota., Murphy SJ; Center for Individualized Medicine, Biomarker Discovery Group, Mayo Clinic, Rochester, Minnesota., Ren H; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota., Serla VV; Center for Individualized Medicine, Biomarker Discovery Group, Mayo Clinic, Rochester, Minnesota., Schaefer Klein JL; Center for Individualized Medicine, Biomarker Discovery Group, Mayo Clinic, Rochester, Minnesota., Karagouga G; Center for Individualized Medicine, Biomarker Discovery Group, Mayo Clinic, Rochester, Minnesota., Harris FR; Center for Individualized Medicine, Biomarker Discovery Group, Mayo Clinic, Rochester, Minnesota., Sosa C; Center for Individualized Medicine, Biomarker Discovery Group, Mayo Clinic, Rochester, Minnesota., Johnson SH; Center for Individualized Medicine, Biomarker Discovery Group, Mayo Clinic, Rochester, Minnesota., Nevala W; Department of Immunology, Mayo Clinic, Rochester, Minnesota., Markovic SN; Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota., Bungum AO; Division of Pulmonary Medicine and Critical Care, Mayo Clinic, Rochester, Minnesota., Edell ES; Division of Pulmonary Medicine and Critical Care, Mayo Clinic, Rochester, Minnesota., Dong H; Department of Immunology, Mayo Clinic, Rochester, Minnesota; Department of Urology, Mayo Clinic, Rochester, Minnesota., Cheville JC; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota., Aubry MC; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota., Jen J; Medical Genome Facility, Mayo Clinic, Rochester, Minnesota., Vasmatzis G; Center for Individualized Medicine, Biomarker Discovery Group, Mayo Clinic, Rochester, Minnesota. Electronic address: vasmatzis.george@mayo.edu. |
| المصدر: | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer [J Thorac Oncol] 2019 Feb; Vol. 14 (2), pp. 276-287. Date of Electronic Publication: 2018 Oct 10. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 101274235 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1556-1380 (Electronic) Linking ISSN: 15560864 NLM ISO Abbreviation: J Thorac Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2016- : New York, NY : Elsevier Original Publication: Hagerstown, MD : Lippincott Williams & Wilkins, c2006- |
| مواضيع طبية MeSH: | Chromothripsis*, Antigens/*genetics , Mesothelioma/*genetics , Pleural Neoplasms/*genetics , Transcriptome/*genetics, Clonal Selection, Antigen-Mediated ; Computer Simulation ; DNA, Neoplasm/analysis ; Gene Dosage ; Gene Rearrangement ; Genomics ; HLA-A Antigens/genetics ; HLA-B Antigens/genetics ; Humans ; Lymphocytes, Tumor-Infiltrating ; Mesothelioma/pathology ; Peptides/genetics ; Peptides/immunology ; Pleural Neoplasms/pathology ; Receptors, Antigen, T-Cell/genetics ; Sequence Analysis, DNA/methods ; Sequence Analysis, RNA ; Survival Rate ; T-Lymphocytes/immunology |
| مستخلص: | Introduction: Malignant pleural mesothelioma is a disease primarily associated with exposure to the carcinogen asbestos. Whereas other carcinogen-related tumors are associated with a high tumor mutation burden, mesothelioma is not. We sought to resolve this discrepancy. Methods: We used mate-pair (n = 22), RNA (n = 28), and T cell receptor sequencing along with in silico predictions and immunologic assays to understand how structural variants of chromosomes affect the transcriptome. Results: We observed that inter- or intrachromosomal rearrangements were present in every specimen and were frequently in a pattern of chromoanagenesis such as chromoplexy or chromothripsis. Transcription of rearrangement-related junctions was predicted to result in many potential neoantigens, some of which were proven to bind patient-specific major histocompatibility complex molecules and to expand intratumoral T cell clones. T cells responsive to these predicted neoantigens were also present in a patient's circulating T cell repertoire. Analysis of genomic array data from the mesothelioma cohort in The Cancer Genome Atlas suggested that multiple chromothriptic-like events negatively impact survival. Conclusions: Our findings represent the discovery of potential neoantigen expression driven by structural chromosomal rearrangements. These results may have implications for the development of novel immunotherapeutic strategies and the selection of patients to receive immunotherapies. (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.) |
| التعليقات: | Comment in: J Thorac Oncol. 2019 Feb;14(2):157-159. (PMID: 30598368) |
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| معلومات مُعتمدة: | K12 CA090628 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: Chromoplexy; Chromosomal rearrangements; Chromothripsis; Mesothelioma; Neoantigens |
| المشرفين على المادة: | 0 (Antigens) 0 (DNA, Neoplasm) 0 (HLA-A Antigens) 0 (HLA-B Antigens) 0 (Peptides) 0 (Receptors, Antigen, T-Cell) |
| تواريخ الأحداث: | Date Created: 20181014 Date Completed: 20200408 Latest Revision: 20200408 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC6348045 |
| DOI: | 10.1016/j.jtho.2018.10.001 |
| PMID: | 30316012 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1556-1380 |
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| DOI: | 10.1016/j.jtho.2018.10.001 |