تقرير
Genomic profiling of post-transplant lymphoproliferative disorders using cell-free DNA.
| العنوان: | Genomic profiling of post-transplant lymphoproliferative disorders using cell-free DNA. |
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| المؤلفون: | Veltmaat N; Department of Hematology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., Zhong Y; Department of Pathology and Medical Biology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., de Jesus FM; Medical Imaging Center, Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., Tan GW; Department of Pathology and Medical Biology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., Bult JAA; Department of Hematology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., Terpstra MM; Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., Mutsaers PGNJ; Department of Hematology, Erasmus Medical Centre Rotterdam, Rotterdam, The Netherlands., Stevens WBC; Department of Hematology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands., Mous R; Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands., Vermaat JSP; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands., Chamuleau MED; Department of Hematology, Amsterdam University Medical Center, Amsterdam, The Netherlands., Noordzij W; Medical Imaging Center, Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., Verschuuren EAM; Department of Pulmonology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., Kok K; Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., Kluiver JL; Department of Pathology and Medical Biology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., Diepstra A; Department of Pathology and Medical Biology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., Plattel WJ; Department of Hematology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., van den Berg A; Department of Pathology and Medical Biology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., Nijland M; Department of Hematology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. m.nijland@umcg.nl. |
| المصدر: | Journal of hematology & oncology [J Hematol Oncol] 2023 Sep 14; Vol. 16 (1), pp. 104. Date of Electronic Publication: 2023 Sep 14. |
| نوع المنشور: | Multicenter Study; Observational Study; Letter; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Biomed Central Country of Publication: England NLM ID: 101468937 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-8722 (Electronic) Linking ISSN: 17568722 NLM ISO Abbreviation: J Hematol Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [London] : Biomed Central, 2008- |
| مواضيع طبية MeSH: | Epstein-Barr Virus Infections*/genetics , Lymphoproliferative Disorders*/genetics , Cell-Free Nucleic Acids*/genetics, Humans ; DNA Copy Number Variations ; Epigenesis, Genetic ; Herpesvirus 4, Human/genetics ; Genomics |
| مستخلص: | Diagnosing post-transplant lymphoproliferative disorder (PTLD) is challenging and often requires invasive procedures. Analyses of cell-free DNA (cfDNA) isolated from plasma is minimally invasive and highly effective for genomic profiling of tumors. We studied the feasibility of using cfDNA to profile PTLD and explore its potential to serve as a screening tool. We included seventeen patients with monomorphic PTLD after solid organ transplantation in this multi-center observational cohort study. We used low-coverage whole genome sequencing (lcWGS) to detect copy number variations (CNVs) and targeted next-generation sequencing (NGS) to identify Epstein-Barr virus (EBV) DNA load and somatic single nucleotide variants (SNVs) in cfDNA from plasma. Seven out of seventeen (41%) patients had EBV-positive tumors, and 13/17 (76%) had stage IV disease. Nine out of seventeen (56%) patients showed CNVs in cfDNA, with more CNVs in EBV-negative cases. Recurrent gains were detected for 3q, 11q, and 18q. Recurrent losses were observed at 6q. The fraction of EBV reads in cfDNA from EBV-positive patients was 3-log higher compared to controls and EBV-negative patients. 289 SNVs were identified, with a median of 19 per sample. SNV burden correlated significantly with lactate dehydrogenase levels. Similar SNV burdens were observed in EBV-negative and EBV-positive PTLD. The most commonly mutated genes were TP53 and KMT2D (41%), followed by SPEN, TET2 (35%), and ARID1A, IGLL5, and PIM1 (29%), indicating DNA damage response, epigenetic regulation, and B-cell signaling/NFkB pathways as drivers of PTLD. Overall, CNVs were more prevalent in EBV-negative lymphoma, while no difference was observed in the number of SNVs. Our data indicated the potential of analyzing cfDNA as a tool for PTLD screening and response monitoring. (© 2023. BioMed Central Ltd., part of Springer Nature.) |
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| فهرسة مساهمة: | Keywords: Cell-free DNA; Copy number variation; Epstein–Barr virus; Genomic profiling; Liquid biopsy; Low-coverage whole genome sequencing; Next generation sequencing; Post-transplant lymphoproliferative disorder; Single nucleotide variants |
| المشرفين على المادة: | 0 (Cell-Free Nucleic Acids) |
| تواريخ الأحداث: | Date Created: 20230913 Date Completed: 20230915 Latest Revision: 20231120 |
| رمز التحديث: | 20231120 |
| مُعرف محوري في PubMed: | PMC10500745 |
| DOI: | 10.1186/s13045-023-01500-x |
| PMID: | 37705050 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1756-8722 |
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| DOI: | 10.1186/s13045-023-01500-x |