Absence of post-transcription RNA modifications of BCL10 in human malignant mesothelioma and colorectal cancer

The BCL10 gene, located at 1p22, has been implicated in a number of human m alignancies, including malignant mesotheliomas (MMs) and colorectal carcino mas. Subsequent reports, however, have revealed an absence of BCL10 mutatio ns in genomic DNA from such tumors. It has been proposed that some abnormal ities of this gene may be found only in RNA and not in genomic DNA, suggest ing that BCL10 may be mutated post-transcriptionally, rather than at the ge nomic level. To explore this possibility, we performed SSCP mutation analys is and direct sequencing of cDNA from 17 MM cell lines displaying LOH in 1p 22, 12 MM tumor specimens, and 11 colon carcinoma cell lines. SSCP revealed several different band shifts in these samples. The nucleotide changes obs erved in the cDNA samples were also seen in matched genomic DNA and corresp onded to known polymorphisms in the general population. Thus, we conclude t he BCL10 mutations are absent at the cDNA level, and that this gene does no t undergo "molecular misreading." Since BCL10 also does not possess mutatio ns at the genomic DNA level, it can be ruled out as a gene involved in the pathogenesis of MM and colorectal cancer. (C) 2001 Wiley-Liss, Inc.