Comparative sequence analysis of a region on human chromosome 13q14, frequently deleted in B-cell chronic lymphocytic leukemia, and its homologous region on mouse chromosome 14

Previous studies have indicated the presence of a putative tumor suppressor gene on human chromosome 13q14, commonly deleted in patients with B-cell c hronic lymphocytic leukemia (B-CLL). We have recently identified a minimall y deleted region encompassing parts of two adjacent genes, termed LEU1 and LEU2 (leukemia-associated genes 1 and 2), and several additional transcript s. In addition, 50 kb centromeric to this region we have identified another gene, LEU5/RFP2. To elucidate further the complex genomic organization of this region, we have identified, mapped, and sequenced the homologous regio n in the mouse. Fluorescence in situ hybridization analysis demonstrated th at the region maps to mouse chromosome 14. The overall organization and gen e order in this region were found to be highly conserved in the mouse. Sequ ence comparison between the human deletion hotspot region and its homologou s mouse region revealed a high degree of sequence conservation with an over all score of 74%. However, our data also show that in terms of transcribed sequences, only two of those, human LEU2 and LEU5/RFP2, are clearly conserv ed, strengthening the case for these genes as putative candidate B-CLL tumo r suppressor genes. (C) 2000 Academic Press.