Mutational Analysis of Genetic Instability in Cell Lines Established from BRCA1 and 2 Carriers.

摘要

The BRCA1 and BRCA2 genes have been implicated in the DNA repair processes that remediate damage resulting from ionizing radiation, a known risk factor for breast cancer. We have identified and/or acquired 5 established lymphoblastoid cell lines from BRCA1 carriers, 4 from BRCA2 carriers, and 9 control normal lines, all chosen so as to reflect a diversity in age of the individual when the original blood sample was drawn. To date, replicated drug selection clonogenic mutation assays at the X-linked HPRT reporter gene have been completed on 4 BRCA1 cell lines and 5 control cell lines. The average (I standard deviation) mutation frequency of the control cell lines was 11.4 + 9.0 x 10(exp -6), in good agreement with published studies. The average mutation frequency for the cell lines from BRCA1 carriers was 17.7 +/- 3.8 x lO(exp -6), which was not significantly higher than that of the controls (p = 0.23) . These data suggest that inheritance of an inactivating mutation in the BRCA1 gene does not inherently lead to an increased frequency of spontaneous mutation, and therefore a lack of DNA repair capacity is not responsible for their predisposition to breast cancer.