Tumor Supressor Genes in Early Breast Cancer and its Progression
Abstract
Ductal carcinoma in situ (DCIS) is a pre-invasive stage of breast cancer. From our allelotyping study of DCIS, chromosomal regions of 8p, 13q, 16q, 17p and 17q showed loss of heterozygosity (LOH) significantly above background (5%). We concentrated our efforts on the LOH mapping of a region on 8p (30% LOH) and identified the smallest common deletion region located at 8p22-p23 in an ^ 1.4 cM interval. An integrated YAC/BAC clone contig covering the deletion region was constructed using CITB and RPCI-11 BAC libraries and the publicly available YAC contig information. STSs (sequence tagged sites) developed from CITB BACs and the publicly available insert end sequences from RPCI-11 BACs on the contig were used for database search. Seven clones with full working draft sequences were identified and localized to the contig. Clone RPCI-11 184021 contains genomic sequence for the tyrosine kinase, blk. A second predicted gene in the same clone shows 89% homology to hematopoietic cell kinase (Hck), a member of the Src family of tyrosine kinases. Clone RPCI-11589N15 contains sequences homologous to human procathepsin B, Squalene synthase and GATA-4. When the sequence of the entire deletion region becomes available, gene-finding programs can be used to identify all genes in this region and assess the likelihood of a gene being a tumor suppressor gene (TSG). Then, the putative TSGs can be evaluated on normal and tumor tissues of DCIS cases.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA391328
Entities
People
- Alison M. Goate
Organizations
- University of Washington