Evidence for in the appearance of mRNAs of nucleotide excision repair genes, in human ovarian cancer tissues.

Nucleotide excision repair (NER) is the DNA repair pathway through which cisplatin-DNA intrastrand adduct is repaired. Clinical studies have shown that increased mRNA expression of selected genes involved in the rate-limiting step of NER, appear to be closely associated with clinical resistance to platinum agents. These specific studies have led to the possibility of an assessment of the order in which, the appearance of mRNAs of selected NER genes may occur. Included in this assessment are ERCC1, XPB, CSB, and XPA, studied in 28 ovarian cancer tumor tissue specimens. The study of these four genes, in pairs, from 28 ovarian cancer specimens, results in 168 separate observations. Based on the mRNA expression patterns of these genes in these tissues, it is suggested that ERCC1 mRNA may appear before the mRNA of any of the other genes, in an obligate fashion. This is followed by XPB mRNA; which appears before the mRNA of XPA; which in turn, may appear before CSB. This pattern is consistent with what we have reported previously, in non-malignant human bone marrow specimens from a cohort of 52 patients.