B-cell neoplasia associated gene with multiple splicing (BCMS): the candidate B-CLL gene on 13q14 comprises more than 560 kb covering all critical regions

Deletions in chromosomal band 13q14.3 occur in > 50% of B-cell chronic lymp hocytic leukemias (B-CLL) and mantle cell lymphoma, indicating the localiza tion of a tumor suppressor gene involved in the pathomechanism of these dis eases. Within a 400 kb recurrently deleted segment at least two minimally d eleted subregions had been reported. For the two genes residing in the prox imal subregion, initially named LEU1 and LEU2, a pathogenic role has not ye t been established. We report here that LEU1 is only a small portion of a l arge gene, which spans all previously reported critical subregions includin g the distal subregion. This gene, designated B-cell neoplasia-associated g ene with multiple splicing (BCMS), is composed of at least 50 exons spannin g greater than or equal to 560 kb of genomic DNA and is expressed in more t han 20 RNA splicing variants. While tissue-specific expression of RNA varia nts was observed, there was no evidence for the expression of a variant spe cific for B-CLL. Sequence analysis of the RNA variants suggests that BCMS t ranscripts belong to the group of non-coding RNAs. The alignment of the gen e with all critical subregions provides a strong argument for BCMS being th e most likely candidate for the tumor suppressor gene in 13q14 involved in the leukemogenesis of B-CLL. Due to the limited understanding of functional RNAs, however, it remains difficult to prove the pathogenic role of BCMS.