Mutation analysis of the BCL10 gene in childhood solid malignancies

BCL10, a gene involved in apoptosis signaling, has recently been identified at chromosome 1p22. This gene was found to be mutated in several types of lymphomas and other kinds of solid tumors. Especially in hepatocellular carcinoma, high mutation rates have been reported. These findings suggest that its inactivation may play an important pathogenetic role in tumorigenesis. Furthermore, abnormalities of chromosome 1 where the BCL10 gene is located are a common feature in pediatric solid tumors. Therefore, we analyzed 95 pediatric solid cancers for genomic BCL10 mutations.

Three exons, which encode the whole coding region, were examined in 95 tumor tissues by PCR-SSCP method. Samples revealing aberrant band patterns were subjected to direct sequencing analysis.

A total of six nucleotide changes were detected. Two were in intron 1 (IVS1 + 11C > G, IVS1 + 58G > C) and four were in exons 1 or 3 (Ala5Ser, Leu8Leu, Thr162Met and Gly213Glu). Of four exonic changes, three at codons 5, 162, and 213 resulted in amino acid substitution. In non-tumor tissues, however, similar mutation types were found, suggesting that all nucleotide changes detected were genetic polymorphisms.

This study represents the first genetic analysis of the BCL10 gene in pediatric solid malignant tumors. Our results suggest that BCL10 mutation as a mechanism involved in tumorigenesis is unlikely to be associated with most childhood malignancies.