Novel Targets for the Diagnosis and Treatment of Breast Cancer Identified by Genomic Analysis

摘要

Chromosomal rearrangements which result in localized increases of genetic material are frequent in breast cancer and occur consistently in certain genomic regions. The resulting increase in expression of genes contained within these amplifications contributes to the malignant phenotype. Such amplified genes such as Her2-Neu provide targets for diagnosis and for the development of inhibitory drugs. The purpose of this study is to use novel genomic technologies to find new genes in breast cancer that are both highly amplified and are suitable targets by virtue of the fact that they are membrane- associated (receptors membrane anfigens secretory proteins). The aims of the study are (1) To specify intervals of genomic amplification (amplicons) in primary breast cancer cell lines using genomic microarrays; (2) To prepare a database of membrane- associated genes selected by differential hybridization of RNA prepared from fractionated microsomes; (3) To use the database to select membrane-associated genes that are located within amplicons and measure their expression in the primary cell line using cDNA arrays in order to select those that are upregulated. These genes will provide new insights and reagents for diagnosis and treatment of breast cancer.