The BCL10 gene was recently isolated from the breakpoint region of t(1;14)(p22;q32) in mucosaassociated lymphoid tissue (MALT) lymphomas. Somatic mutations of BCL10 were found in not only t(1;14)-bearing MALT lymphomas, but also a wide range of other tumors. To clarify the actual frequency and spectrum of BCL10 mutations in primary B-cell non-Hodgkin's lymphomas (NHL), we examined a total of 139 NHL cases comprising 25 with MALT lymphomas, 54 with follicular B-cell lymphomas (FCL), and 60 with diffuse large B-cell lymphomas (DLBL). Polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and sequencing analyses led to the identification of four nucleotide changes in FCL and one in DLBL. In contrast, no BCL10 mutations were found in our series of MALT lymphomas. While screening for mutations, we also found three polymorphic sequence variants at codons 5 and 213 and in intron 1 of the BCL10 gene. Our results strongly suggest that somatic mutations of BCL10, if they occur at all, are rare in B-cell NHLs and do not commonly contribute to their molecular pathogenesis.
Key words: Chromosome translocation -Apoptosis -SSCP -Malignant lymphomaRecurrent chromosomal translocations are well recognized and have been extensively characterized in nodal Bcell lymphomas.1, 2) These translocations were found to involve and deregulate an impressive list of proto-oncogenes including BCL1, BCL2, BCL6, and c-myc. In contrast, data on the molecular genetic mechanisms underlying the pathogenesis of marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type are only now beginning to emerge. Recurrent abnormalities found in MALT lymphomas include trisomies of chromosomes 3, 7, 12, and 18, the t(1;14)(p22;q32), and the t(11;18)(q21;q21).3-9) The t(11;18) translocation is reported to be one of the most frequent and specific chromosomal translocations in MALT lymphomas 7-9) and a novel gene, named MALT1 or MLT, has recently been cloned by ourselves and others from the breakpoint of the t(11;18). [10][11][12] On the other hand, the frequency of the t(1;14) translocation is relatively low and this translocation appears to be characteristic of aggressive MALT lymphomas.
13)The BCL10 gene has been isolated from the breakpoint region of the t(1;14) in MALT lymphomas.14, 15) BCL10, also called CIPER or CARMEN, was found to be a cellular homolog of the equine herpesvirus-2 E10 gene: both contain an amino-terminal caspase recruitment domain (CARD), which is homologous to that found in several apoptotic molecules.14-17) By analogy to BCL2 involvement in follicular B-cell lymphomas (FCL), BCL10 was expected to be anti-apoptotic. In functional assays, however, wild-type BCL10 turned out to be pro-apoptotic. It is noteworthy that BCL10 in t(1;14)-bearing MALT lymphomas exhibited a variety of truncating mutations.14, 15) As expected, the truncated BCL10 was shown to lose its proapoptotic action and display a gain-of-function transforming activity, so that it is conceivable that such mutations may confer a surviva...