Genomic organization and chromosomal mapping of SPARC-like 1, a gene down regulated in cancers

Human SPARC-like 1 (SPARCL1), also known as MAST9 or hevin, is a member of the SPARC protein family. Originally we identified, SPARCL1 as one of the g enes down regulated in human non-small cell lung cancer (NSCLC). Recent rep orts indicate that the down regulation of SPARCL1 also occurs in prostate a nd colon carcinomas, suggesting that SPARCL1 inactivation is a common event not only in NSCLCs but also in other tumors of epithelial origin. In the p resent work we report the cloning and mapping of the genomic locus of human SPARCL1. Using fluorescence in situ hybridization analysis, SPARCL1 was lo calized to chromosome 4q22-25, a region often deleted in human cancers. Fur thermore, we show that the intron/exon organization of the human SPARCL1 ge ne is similar to its murine homologue SC1. SPARCL1 contains 11 exons and 10 introns which span similar to 47 kb of the genome. We also sequenced the 5 '-flanking region of the human SPARCL1 gene containing 2.4 kb of the putati ve promoter region. The data presented herein are a prerequisite for deleti on/mutation analysis of the SPARCL1 gene in tumors. In addition, knowledge of the SPARCL1 promoter sequence allows to investigate the regulation of SP ARCL1 expression on the transcriptional level. Taken together our results w ill help to clarify the function of SPARCL1 in tumor formation.