Cellular markers based on DNA repair (BER, MMR) expression of MLH1, MSH2, FasR and death of lymphocytes as predictive parameters for clinical response to chemotherapy of melanoma patients

Melanoma is a highly aggressive tumor of melanocytes. The efficacy of different cytotoxic chemotherapy regimens does not exceed 20%. The search for markers for patient sensitivity to chemotherapy provides a rational basis for the development of cytotoxic chemotherapy. In this study, we evaluated six blood lymphocyte parameters (the efficacy of BER and MMR; the expression of MLH1, MSH2, FasR; and cell death) as prognostic markers for melanoma chemotherapy. We found that chemotherapy induced AP sites and ssDNA breaks in lymphocytes repaired through the BER pathway. However, ssDNA breaks were completely repaired after chemotherapy and, therefore, did not contribute to the toxic effect of chemotherapy. dsDNA breaks produced by a functioning MMR system appeared downstream of methylation adducts, which was confirmed by the linear correlation of these parameters in various patients. The number of dsDNA breaks, but not MMR, MLH1, and MSH2 expression, correlated to the efficacy of chemotherapy. A positive correlation was observed between lymphocyte death induced by chemotherapy and the patient’s clinical response, which may show that the nucleotide excision repair (NER) mechanism is implicated in the generation of double-strand breaks and the cytotoxic effect of chemotherapy.