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

Author:

Wagener Rabea12,Seufert Julian34,Raimondi Francesco5,Bens Susanne12,Kleinheinz Kortine67,Nagel Inga28,Altmüller Janine9,Thiele Holger10,Hübschmann Daniel711ORCID,Kohler Christian W.12,Nürnberg Peter9,Au-Yeung Rex13ORCID,Burkhardt Birgit14,Horn Heike15,Leoncini Lorenzo16,Jaffe Elaine S.17,Ott German15,Rymkiewicz Grzegorz18,Schlesner Matthias3ORCID,Russell Robert B.5ORCID,Klapper Wolfram13,Siebert Reiner12

Affiliation:

1. Institute of Human Genetics, Ulm University and Ulm University Medical Center, Ulm, Germany;

2. Institute of Human Genetics, Christian-Albrechts University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany;

3. Bioinformatics and Omics Data Analytics, German Cancer Research Center (DKFZ), Heidelberg, Germany;

4. Faculty of Biosciences,

5. Cell Networks, Bioquant, and

6. Institute of Pharmacy and Molecular Biotechnology and Bioquant, University of Heidelberg, Heidelberg, Germany;

7. Division of Theoretical Bioinformatics, DKFZ, Heidelberg, Germany;

8. Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany;

9. Cologne Center for Genomics, Center for Molecular Medicine Cologne and

10. Cologne Center for Genomics, University of Cologne, Cologne, Germany;

11. Department of Pediatric Immunology, Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany;

12. Institute of Functional Genomics, University of Regensburg, Regensburg, Germany;

13. Hematopathology Section, Christian-Albrechts University, Kiel, Germany;

14. Department of Pediatric Hematology and Oncology and NHL-BFM Study Center, University Hospital Münster, Münster, Germany;

15. Department of Clinical Pathology, Robert-Bosch Krankenhaus, and Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany;

16. Section of Pathology, Department of Medical Biotechnology, University of Siena, Siena, Italy;

17. Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; and

18. Flow Cytometry Laboratory, Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute–Oncology Center, Warsaw, Poland

Abstract

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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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