The different epidemiologic subtypes of Burkitt lymphoma share a homogenous micro RNA profile distinct from diffuse large B-cell lymphoma

Lenze, Dido; Leoncini, Lorenzo; Hummel, Michael; Volinia, Stefano; Liu, Chang–Gong; Amato, Teresa; Falco, Giulia De; Githanga, Jessie; Horn, Heike; Nyagol, Joshua; Ott, German; Palatini, Jeff; Pfreundschuh, Michael; Rogena, Emily; Rosenwald, Andreas; Siebert, Reiner; Croce, Carlo M.; Stein, Harald

doi:10.1038/leu.2011.156

Cited by 109 publications

(83 citation statements)

References 54 publications

(72 reference statements)

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“…These results are in agreement with a recent study performed by Lenze et al in which the MYC-negative BL cases did not show downregulation of this microRNA. 46 It is remarkable that this microRNA is located in a region of gain in 6 of the 7 cases with 11q aberration studied.…”

Section: Discussionmentioning

confidence: 99%

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

Salaverría

Martín-Guerrero

Wagener

et al. 2014

Blood

184

133

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Key Points• 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.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 highlevel 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

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Section: Discussionmentioning

confidence: 99%

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

Salaverría

Martín-Guerrero

Wagener

et al. 2014

Blood

184

133

View full text Add to dashboard Cite

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“…Although differences in the average number of hypervariable region mutations and small differences between the gene expression pattern of equatorial African and European BL have suggested that there may be differences in the pathogenesis of these tumours (Piccaluga et al, 2011), the most recent miRNA profiling data suggests that the three subtypes of BL are very similar to each other, while clearly differing from diffuse large B cell lymphoma (Lenze et al, 2011). Thus, BL could almost be defined as a tumour arising in germinal centre cells about to enter, or possibly already within the memory B cell compartment, that are driven by ectopic MYC expression, which, in turn, is usually, but not always, the consequence of a chromosomal translocation involving immunoglobulin genes (heavy or light) and MYC.…”

Section: Other Environmental Factors Implicated In Pathogenesismentioning

confidence: 99%

Epidemiology: clues to the pathogenesis of Burkitt lymphoma

2012

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SummaryThe two major epidemiological clues to the pathogenesis of Burkitt lymphoma (BL) are the geographical association with malaria -BL incidence relates to the malaria transmission rate -and early infection by Epstein-Barr virus (EBV). Both agents cause B cell hyperplasia, which is almost certainly an essential component of lymphomagenesis in BL. The critical event in lymphomagenesis is the creation of a MYC translocation, bringing the MYC gene into juxtaposition with immunoglobulin genes and causing its ectopic expression, thereby driving the proliferation of BL cells. It is highly likely that such translocations are mediated by the activation-induced cytidine deaminase (AID) gene, which is responsible for hypervariable region mutations as well as class switching. Stimulation of the Toll-like receptor 9 by malaria-associated agonists induces AID, providing a mechanism whereby malaria could directly influence BL pathogenesis. EBV-containing cells must reach the memory cell compartment in order to survive throughout the life of the individual, which probably requires traversal of the germinal centre. Normally, cells that do not produce high affinity antibodies do not survive this passage, and are induced to undergo apoptosis. EBV, however, prevents this, and in doing so may also enhance the likelihood of survival of rare translocation-containing cells.

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“…Versus FL, MCL, and CLL with splenic involvement miR-29c NMZL Up Craig et al (60) Versus lymph node with reactive lymphoid hyperplasia FL Down Karube et al (57) t(14;18)-negative cases miR-30a BL Down Lenze et al (34) Versus DLBCL miR-30b cHL Down Navarro et al (73) Versus reactive lymph nodes miR-30d BL Down Lenze et al (34) Versus DLBCL miR-31 ATL Down NIK ⁄ NF-kB Bellon et al (53) Versus CD4+ cells cHL Down Navarro et al (73) Versus reactive lymph nodes miR-34a DLBCL Up FOXP1 Liu (59) Associated with transformation from gastric MALT to DLBCL miR-96 cHL EBV+ Down Navarro et al (73) Versus EBV-negative cHL miR-101 FL Down Karube et al (57) t(14;18)-negative cases ALCL Down Merkel et al (30) Inhibition of prolifelation in ALK(+) type (cell lines) miR-125b DLBCL Up IRF4, BLIMP1 Malumbres et al (26) in GC-enriched cells miR-128a ⁄ b cHL EBV+ Down Navarro et al (73) Versus EBV-negative cHL miR-135a cHL Down JAK2 Navarro et al (73,76) Versus reactive pymph nodes, poor outcome miR-142-3p NK ⁄ T EBV+ Down IL1A Motsch et al (77) Versus NK ⁄ T EBV(À) cells ATL Up Yin et al (52) Versus HTLV1 infected cells, versus CD4+ cells (34) Versus DLBCL MALT(gastric) Up TP53INP1 Saito et al (78) Poor reactivity to H. pylori eradication therapy miR-146a BL Down Lenze et al (34) Versus DLBCL NK ⁄ T -TRAF6 Paik et al (79) Low miR-146a patients have poor prognosis DLBCL(ABC) Up Malumbres et al (26) Versus GCB DLBCL (cell line) miR-146b BL Down Lenze et al (34) Versus DLBCL DLBCL(ABC) Up Malumbres et al (26) Versus GCB DLBCL (cell line) miR-150 MCL Down Be a et al (37) Versus CD19+ or IgD B-cells NK ⁄ T Down DKC1, AKT2 Yamanaka et al (47) Versus CD56 cells cHL Down Gibcus et al (70) Versus NHL PCMZL Down Mons alvez et al (80) Inferior PFS miR-155 MCL Up Be a et al (37) Versus CD19+ or IgD B-cells BL Down AID Kluiver et al…”

Section: Microrna Dysregulation Strongly Contributes the Pathogenesismentioning

confidence: 99%

Role of microRNA in the pathogenesis of malignant lymphoma

2013

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MicroRNA (miRNA) are non-coding regulatory RNA usually consisting of 20À24 nucleotides. Over the past decade, increases and decreases in miRNA expression have been shown to associate with various types of disease, including cancer. The first two known miRNA aberrations resulted from altered expression of DLEU2 and C13orf25 in hematological malignancies. DLEU2, which encodes miR-15a and miR-16-1, was discovered from 13q14 deletion in chronic lymphocytic leukemia, while C13orf25, which encodes six mature miRNA (miR-17, miR-18, miR-19a, miR-19b, miR-20a and miR-92a), was identified from 13q31 amplification in aggressive B-cell lymphomas. These miRNA were downregulated or upregulated in accordance with genomic deletion or amplification, which suggests that they contribute to tumorigenesis through altered regulation of target oncogenes or tumor suppressors. Consistent with that idea, miR-15a ⁄ 16-1 is known to regulate Bcl2 in chronic lymphocytic leukemia, and miR-17-92 regulates the tumor suppressors p21, Pten and Bim in aggressive B-cell lymphomas. Dysregulation of other miRNA, including miR-21, miR-29, miR-150 and miR-155, have also been shown to play crucial roles in the pathogenesis of aggressive transformed, high-grade and refractory lymphomas. Addition of miRNA dysregulation to the original genetic events likely enhances tumorigenicity of malignant lymphoma through activation of one or more signaling pathways. (Cancer Sci 2013; 104: 801-809)

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The different epidemiologic subtypes of Burkitt lymphoma share a homogenous micro RNA profile distinct from diffuse large B-cell lymphoma

Cited by 109 publications

References 54 publications

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

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

Epidemiology: clues to the pathogenesis of Burkitt lymphoma

Role of microRNA in the pathogenesis of malignant lymphoma

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