Recent Advances in the Identification of Genetic and Biochemical Components of Breast Cancer Predisposition

M.   K.   Sauer

doi:10.2174/1389202023350264

Abstract

Breast cancer is one of the most common malignancies affecting women; thus, much effort has been put into understanding the genetics of predisposition to breast cancer as well as identifying factors involved in tumor progression and cancer prognosis. Conventional genetics was used to map and clone the two breast / ovarian cancer predisposition genes, BRCA1 and BRCA2. However, the vast majority of breast cancer cases are of a sporadic nature, likely due to a combination of environmental and genetic factors. Other genes have been identified via the analysis of protein interactions, screens based on inverse genomics, yeast two-hybrid assays, far Westerns, GST-pull downs and chromatography / mass spectrometry have been used to identify a number of proteins that interact with BRCA1 or BRCA2. Biological characteristics such as expression levels, protein stability and phosphorylation as well as the biological roles of the BRCA proteins in DNA repair and transcription have also led to the identification of o ther proteins involved in breast cancer. Recent advances in microarray analysis have allowed the identification of further genetic factors by comparing the transcription profiles of cell lines with varying levels of BRCA1 expression or drug resistance and tumors from patientswith or without BRCA1 / 2 mutations or with different pathobiological types of tumors or prognoses. Additionally, microarray analysis at the DNA level allows for the identification of genes that have been amplified or deleted during cancer progression, and tumor tissue arrays can be used to analyze hundreds of samples simultaneously for the expression of previously identified genetic factors.