Isolation of Genes from Chronosome Region 1p31 Involved in the Development of Breast Cancer
Abstract
Loss of heterozygosity in the 1p3l region is a common event in breast cancer development suggesting the location of a tumor suppressor gene. Using a combination of molecular cloning and bioinformatics strategies, we identified 18 known genes and 16 predicted genes within the critical region of 1p31. Molecular analysis of selected genes such as TTC4 and the progesterone receptor (PTGFR) did not identify nonsense mutations in breast tumors. A comparison of expression profiles for the 18 known genes between tumor and normal tissue demonstrated seven which wee down regulated in breast cancer. No nonsense mutations were found in these genes although protein altering missense mutations were detected specifically in tumor DNA compared with the paired normal tissue. Verification of the rolf of any of these genes in breast cancer will require functional assays. During the course of these analyses, we also identified the CLCA2 gene in 1p31 which was down regulated in 50% of breast cancer and cell lines. Bisulfite secuencing showed that promoter methylation was the cause of the inactivation of this gene and treatment with 5-azacytidine could reactive it in the MDA-NB435 and MDA-MB231 cell lines. These results strongly suggest that CLCA2 could be a critical gene in 1p31 for breast cancer development.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2003
- Accession Number
- ADA421013
Entities
People
- John K. Cowell
Organizations
- Health Research, Incorporated