MALT B cell lymphomas with t(1;14)(p22;q32) showed a recurrent breakpoint upstream of the promoter of a novel gene, Bcl10. Bcl10 is a cellular homolog of the equine herpesvirus-2 E10 gene: both contain an amino-terminal caspase recruitment domain (CARD) homologous to that found in several apoptotic molecules. Bcl10 and E10 activated NF-kappaB but caused apoptosis of 293 cells. Bcl10 expressed in a MALT lymphoma exhibited a frameshift mutation resulting in truncation distal to the CARD. Truncated Bcl10 activated NF-kappaB but did not induce apoptosis. Wild-type Bcl10 suppressed transformation, whereas mutant forms had lost this activity and displayed gain-of-function transforming activity. Similar mutations were detected in other tumor types, indicating that Bcl10 may be commonly involved in the pathogenesis of human malignancy.

Detection of B-cell monoclonality using the polymerase chain reaction (PCR) promises the quick and cost-effective separation of monoclonal from polyclonal B-cell disease. However, the efficiency of the method has yet to be fully assessed, particularly with regard to disease type and selection of PCR primers. We have evaluated two approaches based on amplification of the immunoglobulin heavy chain gene using framework 2 (Fr2) and framework 3 (Fr3) region primers. Frozen tissue samples from 94 cases of low-grade B-cell lymphoma were investigated, all of which had previously been shown to be monoclonal by Southern blot analysis. Using a Fr2 primer, we were able to show monoclonality in 85 per cent of cases; with Fr3, 80 per cent of cases; and using both techniques in separate reactions, 90 per cent of cases. Thus, a significant false-negative rate exists with either primer which can be reduced by using both. We also found a difference in the efficiency of detection in different types of lymphoma; only 87 per cent of mucosa-associated lymphomas and centroblastic/centrocytic lymphomas were shown to be monoclonal, whereas all of the other lymphoma types tested were positive using one or both methods. We conclude that PCR detection of B-cell monoclonality allows rapid analysis of tissue samples, including paraffin-processed material. False-negative results which occur in some types of lymphoma can be reduced by the use of two or more primer combinations.

Genotypic analysis has led to the implication of certain oncogenes in the pathogenesis of specific groups of non-Hodgkin's lymphoma. Rearrangements of c-myc are associated with Burkitt's lymphoma and of bcl-2 with centroblastic/centrocytic lymphoma. Rearrangement of bcl-1 has yet to be associated with a specific group of lymphoma. In this study DNA from 62 cases of low grade B-cell lymphoma, classified using the Kiel classification, were analysed by Southern blotting and hybridization with probes to bcl-1, bcl-2, and c-myc. Rearrangements of bcl-2 were found in a proportion of centroblastic/centrocytic lymphoma comparable to other published studies. Rearrangement of c-myc was not found in any case studied. Bcl-1 rearrangement was found in 2/9 cases of B-CLL, and 3/6 cases of centrocytic lymphoma. This incidence of bcl-1 rearrangement in centrocytic lymphoma suggests that it is a characteristic change. No rearrangement of bcl-1, bcl-2 or c-myc was found in any case of lymphoma of mucosa associated lymphoid tissue (MALT), providing further evidence that, in spite of having a similar morphology to some other groups of low grade B-cell lymphoma, lymphomas of MALT comprise a distinct entity.

Aims-To evaluate polymerase chain reaction (PCR) amplification of T cell receptor (TCR) P and y chain genes as a means of demonstrating monoclonality in T cell lymphomas using histological samples; to compare the performance of PCR with Southern blot analysis.

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High-grade MALT lymphomas often contain low-grade tumour components; both cell populations have been shown to express the same immunoglobulin light chain previously. However, the clonal link between the low and high-grade components has not been established at the genetic level. To investigate this link, we have examined low- and high-grade components micro-dissected from tissue sections of four high-grade gastric MALT lymphomas. PCR and sequence analyses were performed to identify clone-specific rearranged immunoglobulin heavy chain gene sequences. In each of these cases, the PCR products from the two components were identical in size by electrophoresis. Direct sequencing revealed common clone-specific immunoglobulin heavy chain gene rearrangements in both lesions of each case, providing genetic evidence for a clonal link. These results support the proposal that high-grade MALT lymphomas generally evolve from low-grade clones.

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