Human Molecular Genetics, 2001, Vol. 10, No. 12 1275-1285
© 2001 Oxford University Press
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
Abteilung Organisation Komplexer Genome (H0700), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany and 1Innere Medizin III, University of Ulm, Robert-Koch-Strasse 8, D-89081 Ulm, Germany
Deletions in chromosomal band 13q14.3 occur in >50% of B-cell chronic lymphocytic leukemias (B-CLL) and mantle cell lymphoma, indicating the localization of a tumor suppressor gene involved in the pathomechanism of these diseases. Within a 400 kb recurrently deleted segment at least two minimally deleted subregions had been reported. For the two genes residing in the proximal subregion, initially named LEU1 and LEU2, a pathogenic role has not yet been established. We report here that LEU1 is only a small portion of a large gene, which spans all previously reported critical subregions including the distal subregion. This gene, designated B-cell neoplasia-associated gene with multiple splicing (BCMS), is composed of at least 50 exons spanning 
560 kb of genomic DNA and is expressed in more than 20 RNA splicing variants. While tissue-specific expression of RNA variants was observed, there was no evidence for the expression of a variant specific for B-CLL. Sequence analysis of the RNA variants suggests that BCMS transcripts belong to the group of non-coding RNAs. The alignment of the gene with all critical subregions provides a strong argument for BCMS being the 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.
+ These authors contributed equally to this work
To whom correspondence should be addressed. Tel: +49 6221 424619; Fax: +49 6221 424639; Email: p.lichter@dkfz-heidelberg.de
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