Genetic Analysis of DNA Repair Deficiency in Novel Non-Tumor Adjacent and Tumor Cell CulturesSuggests a New Paradigm of Breast Cancer Etiology

Abstract : We have found that 75% of our NTA primary cultures (n= 42) and cell lines manifest the same deficiency of Nucleotide Excision Repair (NER) as the matching tumor culture. This subpopulation of breast cancers indicates that the loss of NER preceded the final mutations that led to full blown transformation. This hypothesis is in stark contrast to the hypothesis that cancer essentially arises in a vacuum and the NTA tissue represents relatively normal tissue. We will use the isogenic pairs of cell lines we have established to determine whether loss of NER in the pairs is: 1. due to reduced expression of the same genes in tumor vs NTA; 2. due to the loss of expression from an epigenetic phenomenon; or 3. due to the loss of expression from a genetic phenomenon, i.e. actual mutation of these genes.