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Blood. 2018 Dec 19. pii: blood-2018-07-864025. doi: 10.1182/blood-2018-07-864025. [Epub ahead of print]

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

Author information

1
Institute of Human Genetics, Ulm University and Ulm University Medical Center, Ulm, Germany.
2
Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.
3
Cell Networks, Bioquant, University of Heidelberg, Heidelberg, Germany.
4
Institute of Pharmacy and Molecular Biotechnology and Bioquant, University of Heidelberg, Heidelberg, Germany.
5
Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Kiel, Germany.
6
Cologne Center for Genomics, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
7
Cologne Center for Genomics, University of Cologne, Cologne, Germany.
8
Department of Pediatric Immunology, Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany.
9
Institute of Functional Genomics, University of Regensburg, Regensburg, Germany.
10
Hematopathology Section, Christian-Albrechts-University, Kiel, Germany.
11
Department of Pediatric Hematology and Oncology and NHL-BFM study center, University Hospital Munster, Munster, Germany.
12
Department of Clinical Pathology, Robert-Bosch Krankenhaus, and Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
13
Section of Pathology, Department of Medical Biotechnology, University of siena, Siena, Italy.
14
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United States.
15
Flow Cytometry Laboratory, Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland.
16
Bioinformatics and Omics Data Analytics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
17
Institute of Human Genetics, Christian-Albrechts University Kiel & University Hospital Schleswig-Holstein, Kiel, Germany reiner.siebert@uni-ulm.de.

Abstract

The new provisional lymphoma category Burkitt-like lymphoma with 11q aberration recently described comprises cases similar to Burkitt lymphoma (BL) on morphological, immunophenotypic and gene expression level 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 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 >3/15 cases). Strikingly, we did not detect recurrent mutations in genes of the ID3-TCF3 axis or 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 7/15 cases. We conclude that the genomic landscape of mnBLL,11q, differs from that of BL both at the chromosomal and mutational level. Our findings implicate that mnBLL,11q, is a lymphoma category distinct from Burkitt lymphoma at the molecular level.

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