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Recurrent 11q aberrations in MYC-neg mature aggressive B-cell lymphomas resembling BL

ABSTRACT: Copy number analysis using Agilent 244k or 180k (Case9) arrays was performed for 8 MYC-negative B-cell lymphomas, with sex-matched control DNAs

ORGANISM(S): Homo sapiens

PROVIDER: GSE47506 | GEO | 2014/01/10

SECONDARY ACCESSION(S): PRJNA205938

REPOSITORIES: GEO

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Recurrent 11q aberrations in MYC-neg mature aggressive B-cell lymphomas resembling BL

Project description:Copy number analysis using Agilent 244k or 180k (Case9) arrays was performed for 8 MYC-negative B-cell lymphomas, with sex-matched control DNAs Agilent 244k (cases 4-7 and 10-12) and 180k (Case9) arrays

2014-01-10 | E-GEOD-47506 | biostudies-arrayexpress

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

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

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

Project 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.

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Project description:The recent characterization of a group of non-MYC rearranged aggressive B-cell lymphomas, resembling Burkitt lymphoma (BL), characteristically harboring a telomeric 11q loss or combined 11q proximal gains/loss pattern has led to the introduction of the provisional entity of Burkitt-like lymphoma with 11q aberration (BLL-11q). Prompted by the discovery of a telomeric 11q loss in an HIV+ high-grade B-cell lymphoma patient, we investigated an extended cohort of aggressive B-cell lymphomas, enriched for cases with histopathological features intermediate between DLBCL and BL, including double- and triple-hit lymphomas (n = 47), for 11q loss/combined 11q proximal gains/loss pattern by fluorescence in situ hybridization. We provide first evidence that 11q aberrations can be found in both BLL in the context of an underlying HIV infection as well as in high-grade B-cell lymphomas with MYC, BCL2, and/or BCL6 rearrangements. We therefore propose that the clinicopathological spectrum of malignancies carrying this aberration may be broader than previously assumed.

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