Isolation of Breast Tumor Suppressor Genes from Chromosome 11p.
Abstract
Genetic alterations of the short arm of chromosome ii are a frequent event in the etiology of cancer. Several childhood and adult tumors demonstrate LOH for lip suggesting the presence of one or more critical tumor suppressor gene(s) involved in several malignancies. We have previously described two regions of frequent allelic loss on the short arm of chromosome 11 in sporadic breast cancer that are likely to harbor tumor suppressor genes. The first interval is bordered by the markers Dl 151318 on the telomeric side and - Dl 154088 on the centromeric side of chromosome 11p15.5. A second, critical region of LOH spans the markers D11s1338-D11s1323 at 11p15.5-p15.4. There is a striking correlation between the loss of the two lip loci and the clinical and histopathological features of breast tumors suggesting that the target genes may contribute to tumor progression and metastasis in breast cancer. Using a combination of EST mapping and gene prediction methods like GRAIL and PowerBlast, we have established transcript maps of LOH regions 1 and 2. We have identified nine novel Unigenes in region 1 and are assessing these genes as candidate tumor suppressors by Northern analysis of normal tissue, normal/tumor breast tissue and breast cancer cell lines. In addition, we are screening tumor samples for mutations by SSCP. We have cloned and characterized a novel gene, HET (Human Efflux Transporter), that is widely expressed in adult and fetal tissues and has homology to known drug-efflux pumps and multi-drug resistance proteins in bacteria. Most fetal tissues show monoallelic expression, suggesting that HET is imprinted. Thus, dosage regulation of the efflux transporter might control fetal growth and altered imprinting could potentially contribute to pathogenesis. Several other novel genes are of particular interest and are currently being assessed as putative tumor suppressors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1998
- Accession Number
- ADA360033
Entities
People
- Ppratima Karnik