In Response to Fakruddin et al. and Apostolou et al

In Response to Fakruddin et al. dicted to result in substitutions of amino acids at the and Apostolou et al. corresponding positions in the protein sequence. In each of these cases, individual tumor DNA samples possessed the same sequence as that of the corresponding cell line. We agree with many of the above findings, including To determine if the divergent sequences represented the frequency and nature of BCL10 polymorphisms. mutations of the BCL10 gene or polymorphisms, a panel However, it appears that some BCL10 abnormalities of 50 normal genomic DNA samples from the general may be found only in RNA and not genomic DNA, sug-population was screened (data not shown). The nucleo-gesting that BCL10 may undergo posttranscriptional se-tide alteration in exon 1 seen in 18 MMs (Table 1) was quence modification. assumed to be a polymorphism, because it was ob-Wild-type BCL10 is proapoptotic and behaves as a served in numerous MMs and a control sample, and it tumor suppressor gene (Koseki et al., 1999; Thome et did not predict an amino acid change. was not studied further. The nucleotide change in exon et al., 1999). BCL10 sequence abnormalities were first 1 (nucleotide 13) of Meso 38 destroys an AciI restriction detected in cDNA clones from a MALT lymphoma with enzyme site. Restriction enzyme analysis revealed that t(1;14) and were unusually heterogeneous. An identical three of 50 samples from the general population do not spectrum of cDNA abnormalities has been detected in possess this AciI site, which corresponds to an allele other t(1;14) MALT lymphomas (Zhang et al., 1999), mak-frequency of 3%. The nucleotide alteration in exon 3 ing it unlikely that all these changes represented RT, (nucleotide 638) of Meso 17 and Meso 59 does not occur PCR, or cloning artifacts. at a restriction enzyme site. Therefore, we performed We initially sequenced cDNA clones from 6 malignant SSCP analysis on these two MMs and 50 normal DNA cell lines, including Tera-1, Tera-2, and GCT-44 and samples. Nine of 50 DNA samples from normal individu-three mesothelioma lines, and in each, BCL10 abnormal-als (allele frequency, 9%) displayed banding patterns ities were detected (Table 2 of Willis et al., 1999). Addi-identical to those observed in Meso 17 and Meso 59 tional cDNA clones from Tera-2, a cell line that exhibits (Table 1). Thus, we conclude that all of the nucleotide differences detected in our MM cell lines and tumors Table 1. Summary of …