MYC translocation-negative classical Burkitt lymphoma cases: an alternative pathogenetic mechanism involving miRNA deregulation.

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.

Histology of specimens taken by prostatectomy and needle biopsy.

OBJECTIVES: To determine the histology of the prostate in prostatectomy done for benign prostatic hypertrology (BPH), and prostate needle biopsy done for raised prostatic specific antigen (PSA). DESIGN: A retrospective study. SETTINGS: Nairobi Hospital, Kenyatta National Hospital and Upper Hill Medical Centre. SUBJECTS: The records of all the patients who had prostatectomy for BPH or trans-rectal needle biopsy of the prostate for raised prostatic specific antigen by the author and whose histology was determined at the Nairobi Hospital between May 2004 and December 2006. RESULTS: A total of 108 specimens from 108 patients were sent to the laboratory. The ages of the patients ranged from 48 years to 83 years with a mean of 71.3 years. Of the 108 specimens submitted 82 were benign prostatic hypertrophy and 26 were carcinoma of the prostate. Out of 78 prostatectomy specimens ten (12.8%) had prostate cancer. In the needle biopsy group 16 out of 30 (53%) had prostate cancer. In total there were 82 (76%) patients with histology of benign prostate enlargement and 26 (24%) with histology of prostate cancer. CONCLUSION: Prostate cancer is a common disease in Kenya and a lot of it is important cancer as it will progress and cause death. In this poor resource setting it is possible to make diagnosis of prostate cancer even in the absence of transrectal ultrasound (TRUS) to help biopsy the prostate. The higher the prostatic specific antigen in asymptomatic patients the higher the yield of prostate cancer on biopsy of the prostate.