The mutational landscape of Burkitt-like lymphoma with 11q aberration is distinct from that of Burkitt lymphoma

Blood - Tập 133 - Trang 962-966 - 2019
Rabea Wagener1,2, Julian Seufert3,4, Francesco Raimondi5, Susanne Bens1,2, Kortine Kleinheinz6,7, Inga Nagel2,8, Janine Altmüller9, Holger Thiele10, Daniel Hübschmann7,11, Christian W. Kohler12, Peter Nürnberg9, Rex Au-Yeung13, Birgit Burkhardt14, Heike Horn15, Lorenzo Leoncini16, Elaine S. Jaffe17, German Ott15, Grzegorz Rymkiewicz18, Matthias Schlesner3, Robert B. Russell5
1Institute of Human Genetics, Ulm University and Ulm University Medical Center, Ulm, Germany
2Institute of Human Genetics, Christian-Albrechts University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
3Bioinformatics and Omics Data Analytics, German Cancer Research Center (DKFZ), Heidelberg, Germany
4Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany
5Cell Networks, Bioquant, University of Heidelberg, Heidelberg, Germany.
6Institute of Pharmacy and Molecular Biotechnology and Bioquant, University of Heidelberg, Heidelberg, Germany
7Division of Theoretical Bioinformatics, DKFZ, Heidelberg, Germany
8Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
9Cologne Center for Genomics, Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
10Cologne Center for Genomics, University of Cologne, Cologne, Germany;
11Department of Pediatric Immunology, Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany
12Institute of Functional Genomics, University of Regensburg, Regensburg, Germany
13Hematopathology Section, Christian-Albrechts University, Kiel, Germany
14Department of Pediatric Hematology and Oncology and NHL-BFM Study Center, University Hospital Münster, Münster, Germany
15Department of Clinical Pathology, Robert-Bosch Krankenhaus, and Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
16Section of Pathology, Department of Medical Biotechnology, University of Siena, Siena, Italy
17Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
18Flow Cytometry Laboratory, Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute–Oncology Center, Warsaw, Poland

Tóm tắt

Abstract The new recently described provisional lymphoma category Burkitt-like lymphoma with 11q aberration comprises cases similar to Burkitt lymphoma (BL) on morphological, immunophenotypic and gene-expression levels but lacking the IG-MYC translocation. They are characterized by a peculiar imbalance pattern on chromosome 11, but the landscape of mutations is not yet described. Thus, we investigated 15 MYC-negative Burkitt-like lymphoma with 11q aberration (mnBLL,11q,) cases by copy-number analysis and whole-exome sequencing. We refined the regions of 11q imbalance and identified the INO80 complex-associated gene NFRKB as a positional candidate in 11q24.3. Next to recurrent gains in 12q13.11-q24.32 and 7q34-qter as well as losses in 13q32.3-q34, we identified 47 genes recurrently affected by protein-changing mutations (each ≥3 of 15 cases). Strikingly, we did not detect recurrent mutations in genes of the ID3-TCF3 axis or the SWI/SNF complex that are frequently altered in BL, or in genes frequently mutated in germinal center–derived B-cell lymphomas like KMT2D or CREBBP. An exception is GNA13, which was mutated in 7 of 15 cases. We conclude that the genomic landscape of mnBLL,11q, differs from that of BL both at the chromosomal and mutational levels. Our findings implicate that mnBLL,11q, is a lymphoma category distinct from BL at the molecular level.

Tài liệu tham khảo

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Blood

Tập 133

962-966

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