Novel Functional Screen for New Breast Cancer Genes

摘要

Genetic instability is a hallmark of tumor development. Mechanisms for maintenance of genomic stability are heterogeneous and identification of the genes responsible a critical goal of cancer biologists. The very large number of genetic alterations in breast tumors and genetic heterogeneity, even within a single breast tumor, strongly suggests that some mutator mechanism must be involved in breast tumorigenesis. Our hypothesis is that a mutator mechanism contributes to the development of breast cancer. However, since breast tumors do not display an obvious phenotype that signals the presence of a mutator defect (such as microsatellite instability), another scheme to identify defects in repair genes and their targets is necessary. Thus, our first objective is to use a novel yeast model system to identify genes that are previously unrecognized targets of mutator mechanisms and to determine whether these genes are altered in breast tumors. Our second objective is to identify genes that function as novel mutators in the yeast system then evaluate whether any are altered in breast tumors. The identification of mutator genes and their targets that contribute to the etiology of breast cancer will enhance our understanding of the genetic mechanisms involved in initiation and progress of disease. These genes will impact drug and biomarker discovery and ultimately, revolutionize patient care.