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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Burkitt lymphoma beyond MYC translocation: N-MYC and DNA methyltransferases dysregulation

Authors: Giulia De Falco, Maria Raffaella Ambrosio, Fabio Fuligni, Anna Onnis, Cristiana Bellan, Bruno Jim Rocca, Mohsen Navari, Maryam Etebari, Lucia Mundo, Sara Gazaneo, Fabio Facchetti, Stefano A. Pileri, Lorenzo Leoncini, Pier Paolo Piccaluga

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

The oncogenic transcription factor MYC is pathologically activated in many human malignancies. A paradigm for MYC dysregulation is offered by Burkitt lymphoma, where chromosomal translocations leading to Immunoglobulin gene-MYC fusion are the crucial initiating oncogenic events. However, Burkitt lymphoma cases with no detectable MYC rearrangement but maintaining MYC expression have been identified and alternative mechanisms can be involved in MYC dysregulation in these cases.

Methods

We studied the microRNA profile of MYC translocation-positive and MYC translocation-negative Burkitt lymphoma cases in order to uncover possible differences at the molecular level. Data was validated at the mRNA and protein level by quantitative Real-Time polymerase chain reaction and immunohistochemistry, respectively.

Results

We identified four microRNAs differentially expressed between the two groups. The impact of these microRNAs on the expression of selected genes was then investigated. Interestingly, in MYC translocation-negative cases we found over-expression of DNA-methyl transferase family members, consistent to hypo-expression of the hsa-miR-29 family. This finding suggests an alternative way for the activation of lymphomagenesis in these cases, based on global changes in methylation landscape, aberrant DNA hypermethylation, lack of epigenetic control on transcription of targeted genes, and increase of genomic instability. In addition, we observed an over-expression of another MYC family gene member, MYCN that may therefore represent a cooperating mechanism of MYC in driving the malignant transformation in those cases lacking an identifiable MYC translocation but expressing the gene at the mRNA and protein levels.

Conclusions

Collectively, our results showed that MYC translocation-positive and MYC translocation-negative Burkitt lymphoma cases are slightly different in terms of microRNA and gene expression. MYC translocation-negative Burkitt lymphoma, similarly to other aggressive B-cell non Hodgkin’s lymphomas, may represent a model to understand the intricate molecular pathway responsible for MYC dysregulation in cancer.
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Metadata
Title
Burkitt lymphoma beyond MYC translocation: N-MYC and DNA methyltransferases dysregulation
Authors
Giulia De Falco
Maria Raffaella Ambrosio
Fabio Fuligni
Anna Onnis
Cristiana Bellan
Bruno Jim Rocca
Mohsen Navari
Maryam Etebari
Lucia Mundo
Sara Gazaneo
Fabio Facchetti
Stefano A. Pileri
Lorenzo Leoncini
Pier Paolo Piccaluga
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1661-7

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