Nucleotide excision repair deficiency is intrinsic in sporadic stage I breast cancer

摘要: The molecular etiology of breast cancer has proven to be remarkably complex. Most individual oncogenes are disregulated in only approximately 30% tumors, indicating that either very few alterations common the majority cancers, or they have not yet been identified. In striking contrast, we now show 19 stage I tumors tested with functional unscheduled DNA synthesis assay exhibited a significant deficiency nucleotide excision repair (NER) capacity relative normal epithelial tissue from disease-free controls (n = 23). Loss capacity, including complex, damage-comprehensive NER pathway, results genomic instability, hallmark carcinogenesis. By microarray analysis, mRNA expression levels for 20 canonical genes were reduced representative tumor samples versus normal. Significant reductions observed these analyzed by more sensitive method RNase protection. These confirmed at protein level five gene products. Taken together, data suggest may play an important role sporadic cancer, and early-stage intrinsically susceptible genotoxic chemotherapeutic agents, such as cis-platinum, whose damage is remediated NER. addition, genes, could provide basis development biomarkers identification tumorigenic epithelium.