Accession Number : ADA333277

Title :   Identification of BRCAl and 2 Other Tumor Suppressor Genes on Chromosome 17 Through Positional Cloning

Descriptive Note : Annual rept 1 Jul 96-30 Jun 97

Corporate Author : UTAH UNIV SALT LAKE CITY

Personal Author(s) : White, Raymond L.

PDF Url : ADA333277

Report Date : JUL 1997

Pagination or Media Count : 24

Abstract : During the past year our project has evolved dramatically and significant progress has been make with respect to our overall goals of defining the genetic changes that distinguish normal cells from tumor cells of the breast. The most important evolution of the project is our change in strategy from identifying presumed tumor suppressor genes defined by loss of heterozygosity (LOH) using a positional cloning approach, to ascertaining and comparing genetic expression profiles from surgical specimens or cells grown in tissue culture using hybridization of cDNA from our tissues to microarrays of interesting genes. This is a very new technology and we are using a novel micro arraying and scanning instrument recently acquired by our laboratory in collaboration with Molecular Dynamics/Amersham. Preliminary experiments suggest that the sensitivity of our new microarray system is sufficiently high to allow us to detect variance in gene expression levels with high precision even under complex hybridization conditions. We have also applied the Differential Display protocol to identify three genes with altered expression in a model system of normal and neoplastic epithelial colonocytes. As an alternative to determining biologic effects of specific genes, we have tested and selected an amphoteric retroviral conditional expression system, which replaces previous experiments using antisense oligo's. We are confident that the 'modernization' of our research project will facilitate the identification of genes critical to the development and progression of breast cancer.

Descriptors :   *CHROMOSOMES, *GENES, *CLONES, *BREAST CANCER, PROTEINS, NEOPLASMS, DEOXYRIBONUCLEIC ACIDS, MUTATIONS, CELLS(BIOLOGY), GENETIC MAPPING, SUPPRESSORS, TISSUE CULTURE, HYBRIDIZATION.

Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE