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Genomic organization and chromosomal mapping of SPARC-like 1, a gene down regulated in cancers
S G Isler1, S Schenk, I Bendik
1Laboratory of Molecular Oncology, Department of Research, University Hospital Basle, CH-4031 Basle, Switzerland.
Abstract:
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 genes down regulated in human non-small cell lung cancer (NSCLC). Recent reports indicate that the down regulation of SPARCL1 also occurs in prostate and colon carcinomas, suggesting that SPARCL1 inactivation is a common event not only in NSCLCs but also in other tumors of epithelial origin. In the present work we report the cloning and mapping of the genomic locus of human SPARCL1. Using fluorescence in situ hybridization analysis, SPARCL1 was localized to chromosome 4q22-25, a region often deleted in human cancers. Furthermore, we show that the intron/exon organization of the human SPARCL1 gene is similar to its murine homologue SC1. SPARCL1 contains 11 exons and 10 introns which span approximately 47 kb of the genome. We also sequenced the 5'-flanking region of the human SPARCL1 gene containing 2.4 kb of the putative promoter region. The data presented herein are a prerequisite for deletion/mutation analysis of the SPARCL1 gene in tumors. In addition, knowledge of the SPARCL1 promoter sequence allows to investigate the regulation of SPARCL1 expression on the transcriptional level. Taken together our results will help to clarify the function of SPARCL1 in tumor formation.
Insights
Human SPARCL1 gene, implicated in lung, prostate, and colon cancers, has been cloned and mapped. Its genomic structure and promoter region were analyzed to understand its role in tumor formation.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- Human SPARC-like 1 (SPARCL1), also known as MAST9 or hevin, is part of the SPARC protein family.
- SPARCL1 is frequently downregulated in non-small cell lung cancer (NSCLC), prostate, and colon carcinomas, suggesting a role in tumorigenesis.
- Tumorigenesis often involves the inactivation of tumor suppressor genes, making SPARCL1 a potential candidate.
Purpose of the Study:
- To clone and map the genomic locus of the human SPARCL1 gene.
- To analyze the intron/exon organization and the 5'-flanking promoter region of SPARCL1.
- To lay the groundwork for investigating SPARCL1's role in cancer through deletion/mutation analysis and transcriptional regulation studies.
Main Methods:
- Fluorescence in situ hybridization (FISH) for gene localization.
- Genomic DNA analysis to determine intron/exon structure.
- DNA sequencing of the 5'-flanking region to identify the promoter.
Main Results:
- The human SPARCL1 gene was successfully cloned and mapped to chromosome 4q22-25, a region frequently deleted in cancers.
- SPARCL1 exhibits an 11-exon, 10-intron structure spanning approximately 47 kb, similar to its murine homologue.
- The 2.4 kb 5'-flanking region, containing the putative promoter, was sequenced.
Conclusions:
- The genomic locus and structure of the human SPARCL1 gene have been elucidated.
- This foundational data is essential for future studies on SPARCL1 deletions and mutations in various cancers.
- Understanding SPARCL1's promoter region will enable investigations into its transcriptional regulation and functional significance in tumor development.