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(l:14)(p22 :q32) of mucosa-associated lymphoid tissue B cell non-Hodgkin lymphoma (MAL Toma). was shown to have frequent somatic mutations and short deletions wit hin the coding region in MALToma and a variety of other lymphomas and solid tumors. These observations have been recently questioned. In this study, w e examined BCL10 gene mutations by direct sequencing of the entire coding r egion of the BCL10 gene, amplified from paired normal and tumor genomic DNA s, as well as tumor cDNAs. in 23 cases of primary gastric B cell non-Hodgki n lymphomas. comprising of 6 cases of MALToma and 17 cases of diffuse large cell (DLC) lymphoma. Heterozygosity due to three types of known polymorphi sms 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 c ases. In one case (4.3%) GIC heterozygosity in codon 8 in normal germline D NA was reduced to homozygosity (LOH) in tumor DNA and cDNA. Mutations inact ivating BCL10 gene product function were not found in any of these cases. M oreover. post-transcriptional alterations were not indicated by abnormaliti es in BCL10 mRNA sequence in tumor cDNAs in these gastric lymphoma cases. O ur results show that somatic mutations in the BCL10 gene rarely occur in ga stric lymphoma and indicate that this gene is unlikely to be of pathogeneti c significance in the majority of gastric lymphomas. (C) 2001 Elsevier Scie nce Inc. All rights reserved.