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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
MYC translocation-negative classical Burkitt lymphoma cases: An alternative pathogenetic mechanism involving miRNA deregulation
Journal of Pathology, Volume 216, No. 4, Year 2008
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Description
The molecular feature of Burkitt lymphoma (BL) is the translocation that places c-Myc under the control of immunoglobulin gene regulatory elements. However, there is accumulating evidence that some cases may lack an identifiable MYC translocation. In addition, during the EUROFISH project, aiming at the standardization of FISH procedures in lymphoma diagnosis, we found that five cases out of 35 classic endemic BLs were negative for MYC translocations by using a split-signal as well as a dual-fusion probe. Here we investigated the expression pattern of miRNAs predicted to target c-Myc, in BL cases, to clarify whether alternative pathogenetic mechanisms may be responsible for lymphomagenesis in cases lacking the MYC translocation. miRNAs are a class of small RNAs that are able to regulate gene expression at the post-transcriptional level. Several studies have reported their involvement in cancer and their association with fragile sites in the genome. They have also been shown to control cell growth, differentiation, and apoptosis, suggesting that these molecules could act as tumour suppressors or oncogenes. Our results demonstrated a modulation of specific miRNAs. In particular, down-regulation of hsa-let-7c was observed in BL cases, compared to normal controls. More interestingly, hsa-mir-34b was found to be down-regulated only in BL cases that were negative for MYC translocation, suggesting that this event might be responsible for c-Myc deregulation in such cases. This hypothesis was further confirmed by our in vitro experiments, which demonstrated that increasing doses of synthetic hsa-mir-34b were able to modulate c-Myc expression. These results indicate for the first time that hsa-mir-34b may influence c-Myc expression in Burkitt lymphoma as the more common aberrant control exercised by the immunoglobulin enhancer locus. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Authors & Co-Authors
Leucci, Eleonora
Italy, Siena
Università Degli Studi Di Siena
Cocco, Mario
Italy, Siena
Università Degli Studi Di Siena
Onnis, Anna
Italy, Siena
Università Degli Studi Di Siena
Giulia De Falco, Giulia
Italy, Siena
Università Degli Studi Di Siena
van Cleef, Patricia H.J.
Netherlands, Nijmegen
Radboud University Medical Center
Bellan, Cristiana
Italy, Siena
Università Degli Studi Di Siena
van Rijk, Anke F.
Netherlands, Nijmegen
Radboud University Medical Center
Nyagol, Joshua Akelo
Italy, Siena
Università Degli Studi Di Siena
Byakika, Bessie
Kenya, Nairobi
Nairobi Hospital
Lazzi, S.
Italy, Siena
Università Degli Studi Di Siena
Tosi, Piero
Italy, Siena
Università Degli Studi Di Siena
Van Krieken, J. Han
Netherlands, Nijmegen
Radboud University Medical Center
Leoncini, L.
Italy, Siena
Università Degli Studi Di Siena
Statistics
Citations: 205
Authors: 13
Affiliations: 3
Identifiers
Doi:
10.1002/path.2410
ISSN:
00223417
e-ISSN:
10969896
Research Areas
Cancer
Genetics And Genomics