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A recurrent 11q aberration pattern characterizes a subset of MYC-negative high-grade B-cell lymphomas resembling Burkitt lymphoma

Blood, 2014-02, Vol.123 (8), p.1187-1198 [Peer Reviewed Journal]

2014 American Society of Hematology ;2014 ;ISSN: 0006-4971 ;EISSN: 1528-0020 ;DOI: 10.1182/blood-2013-06-507996 ;PMID: 24398325

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Title:
A recurrent 11q aberration pattern characterizes a subset of MYC-negative high-grade B-cell lymphomas resembling Burkitt lymphoma
Author: Salaverria, Itziar ; Martin-Guerrero, Idoia ; Wagener, Rabea ; Kreuz, Markus ; Kohler, Christian W. ; Richter, Julia ; Pienkowska-Grela, Barbara ; Adam, Patrick ; Burkhardt, Birgit ; Claviez, Alexander ; Damm-Welk, Christine ; Drexler, Hans G. ; Hummel, Michael ; Jaffe, Elaine S. ; Küppers, Ralf ; Lefebvre, Christine ; Lisfeld, Jasmin ; Löffler, Markus ; Macleod, Roderick A.F. ; Nagel, Inga ; Oschlies, Ilske ; Rosolowski, Maciej ; Russell, Robert B. ; Rymkiewicz, Grzegorz ; Schindler, Detlev ; Schlesner, Matthias ; Scholtysik, René ; Schwaenen, Carsten ; Spang, Rainer ; Szczepanowski, Monika ; Trümper, Lorenz ; Vater, Inga ; Wessendorf, Swen ; Klapper, Wolfram ; Siebert, Reiner
Subjects: Adolescent ; Adult ; Aged ; B-Lymphocytes - physiology ; Burkitt Lymphoma - classification ; Burkitt Lymphoma - genetics ; Burkitt Lymphoma - pathology ; Cell Line ; Child ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 14 ; Chromosomes, Human, Pair 8 ; Female ; Gene Expression Regulation, Neoplastic ; Genes, myc - genetics ; Humans ; Lymphoid Neoplasia ; Male ; Neoplasm Grading ; Recurrence ; Translocation, Genetic - genetics ; Young Adult
Is Part Of: Blood, 2014-02, Vol.123 (8), p.1187-1198
Description: The genetic hallmark of Burkitt lymphoma (BL) is the t(8;14)(q24;q32) and its variants leading to activation of the MYC oncogene. It is a matter of debate whether true BL without MYC translocation exists. Here, we identified 59 lymphomas concordantly called BL by 2 gene expression classifiers among 753 B-cell lymphomas. Only 2 (3%) of these 59 molecular BL lacked a MYC translocation, which both shared a peculiar pattern of chromosome 11q aberration characterized by interstitial gains including 11q23.2-q23.3 and telomeric losses of 11q24.1-qter. We extended our analysis to 17 MYC-negative high-grade B-cell lymphomas with a similar 11q aberration and showed this aberration to be recurrently associated with morphologic and clinical features of BL. The minimal region of gain was defined by high-level amplifications in 11q23.3 and associated with overexpression of genes including PAFAH1B2 on a transcriptional and protein level. The recurrent region of loss contained a focal homozygous deletion in 11q24.2-q24.3 including the ETS1 gene, which was shown to be mutated in 4 of 16 investigated cases. These findings indicate the existence of a molecularly distinct subset of B-cell lymphomas reminiscent of BL, which is characterized by deregulation of genes in 11q. •A subset of lymphomas with gene expression and pathological characteristics of Burkitt lymphomas but absence of MYC translocation does exist.•These lymphomas carry chr 11q proximal gains and telomeric losses, suggesting co-deregulation of oncogenes and tumor suppressor genes.
Publisher: United States: Elsevier Inc
Language: English
Identifier: ISSN: 0006-4971
EISSN: 1528-0020
DOI: 10.1182/blood-2013-06-507996
PMID: 24398325
Source: Geneva Foundation Free Medical Journals at publisher websites
MEDLINE
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A recurrent 11q aberration pattern characterizes a subset of MYC-negative high-grade B-cell lymphomas resembling Burkitt lymphoma

2014 American Society of Hematology ;2014 ;ISSN: 0006-4971 ;EISSN: 1528-0020 ;DOI: 10.1182/blood-2013-06-507996 ;PMID: 24398325

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