Genomic instability and breast cancer

Abstract

The loss of genomic stability is accepted as being one of the most important aspects of cancer. The correlation between genomic instability and cancer proneness in cases of known genetic syndromes (e.g. ataxia telengectasia, Fanconi anemia) is well established. This study was conducted to assess genomic instability in 19 patients with sporadic breast cancer. We used the comet assay on the lymphocytes of patients before radiotherapy and/or chemotherapy. The alkaline comet assay (single-cell gel electrophoresis) is a sensitive and rapid method for detecting DNA damage (single strand breaks and alkali-labile sites) in G(0) cells, at a single-cell level. This assay was achieved in vitro without irradiation and after exposure (dose ranging from 50 cGy to 5 Gy). The results show that the patients have higher baseline values than controls. At 2 Gy, the mean tail moment, score and the percentage of DNA in the tail increase for both groups but these values are much higher for patients. Our results show that the lymphocyte DNA of cancer patients is more damaged than that of controls with or without irradiation. Our hypothesis is that this baseline DNA damage reflect a genomic instability in sporadic breast cancer. This instability seems to increase after in vitro irradiation.