The short arm of chromosome 8 is a site of allele loss in a variety of cancers of epithelial origin, and we have postulated the existence of a tumor suppressor gene (TSG) on this chromosome; there is clinical evidence to suggest that this TSG is involved in tumor progression rather than transformation, and we will take advantage of this activity to develop a biologic assay for the gene. Deletion mapping by us and by others has demonstrated that there exist two distinct Sites of loss of heterozygosity in colorectal cancer; here we propose to study the distal region at 8p22 because it has been implicated in a wide variety of tumor types, including prostate, lung, breast, and colorectal. Overall, we plan to take a positional cloning approach, making use of biologic materials which are relevant to the study. Our studies will span a range of tumor types, but we will continue to focus on colorectal cancer because of our unique materials-colon cancer cell lines which we are establishing-that will facilitate the search for the gene. We have joined forces with Dr. Rob Bookstein, who has made available to us a YAC contig and information on a homozygous deletion in prostate cancer. We are also working with Dr. Carrie Rinker-Schaeffer, who is experienced in a metastasis suppression assay in prostate cancer, that we will apply to our gene.
Our specific aims are: (1) to refine the localization of the 8p22 deletion region, and prepare a complete P1 contig; (2) to develop a biologic assay for the 8p TSG based on suppression of growth or metastases in the Dunning prostate cancer cell lines; (3) to isolate and test candidate genes from the deletion region, using genetic methods as well as biological assays; (4) to begin to characterize this new TSG biologically, including cDNA sequencing and genomic mapping, and mutational analysis of tumors and colon cancer cell lines. This gene is implicated in a number of common cancers such as lung, colon, prostate, and breast; our identification of the gene will be important to understanding the biology of these tumors, which together comprise the overwhelming majority of all cancers in the US today.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA056707-01A5
Application #
2097519
Study Section
Genome Study Section (GNM)
Project Start
1995-09-30
Project End
1995-10-31
Budget Start
1995-09-30
Budget End
1995-10-31
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637