BCL10 somatic mutations rarely occur in gastric lymphoma:: detection of high frequency of polymorphisms in BCL10 coding region

The BCL10 gene, recently isolated due to its involvement in the t(1;14)(p22;q32) of mucosa-associated lymphoid tissue B cell non-Hodgkin lymphoma (MALToma), was shown to have frequent somatic mutations and short deletions within the coding region in MALToma and a variety of other lymphomas and solid tumors. These observations have been recently questioned. In this study, we examined BCL10 gene mutations by direct sequencing of the entire coding region of the BCL10 gene, amplified from paired normal and tumor genomic DNAs, as well as tumor cDNAs, in 23 cases of primary gastric B cell non-Hodgkin lymphomas, comprising of 6 cases of MALToma and 17 cases of diffuse large cell (DLC) lymphoma. Heterozygosity due to three types of known polymorphisms in codon 5 (17.3%), codon 8 (21.7%), and codon 213 (8.6%) were observed in both normal germline DNA and tumor DNAs and tumor cDNAs in individual cases. In one case (4.3%) G/C heterozygosity in codon 8 in normal germline DNA was reduced to homozygosity (LOH) in tumor DNA and cDNA. Mutations inactivating BCL10 gene product function were not found in any of these cases. Moreover, post-transcriptional alterations were not indicated by abnormalities in BCL10 mRNA sequence in tumor cDNAs in these gastric lymphoma cases. Our results show that somatic mutations in the BCL10 gene rarely occur in gastric lymphoma and indicate that this gene is unlikely to be of pathogenetic significance in the majority of gastric lymphomas.