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Dissemination of knowledge and practical implementation of molecular diagnostic assays in the classification of mantle cell lymphoma and patient care

The investigators focused on two aspects of mantle cell lymphoma: the translocation t(11;14) with deregulation of the cyclinD1 gene as a primary genetic abnormality and the occurrence of somatic hypermutations (SHM) in the immunoglobulin (Ig) genes.

- The t(11;14) was studied by polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) assays in CD34+ bone marrow progenitor cells, the mature tumor cells and a case of transformed mantle cell lymphoma. FISH methods included FISH on paraffin tissue sections and Fiction with double staining for CD34. Cyclin D1 expression was measured by quantitative RT-PCR and immunohistochemistry and related to the molecular structure of the translocation.

- Ig gene somatic hypermutations (SHM) were analysed by DNA sequencing and were related to class switch recombination (CSR) attempts and the level of Activation Induced Deaminase (AID), a key protein in the induction of SHM and Ig class switch recombination (CSR).

We conclude that purified CD34+ bone marrow stem cells do not contain the t(11;14) after vigorous depletion of CD20+ cells. This supports the clinical use of anti CD20 antibodies in purging of autologous stem cell. The distribution of BCL1 breakpoints in MCL was slightly different from reported in literature. No correlation between cyclin D1 expression and the position of the breakpoints was observed. In one case of transformed MCL we identified an intact t(11;14) but an additional downstream MYC breakpoint at the functional IgH allele. In one quarter of the MCL cases we found evidence for SHM, however, without any correlation with AID expression or signs of CSR.

Reported by

Groningen University Medical Center / University Hospital Groningen
Hanseplein 1
9713 GZ Groningen
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