Analysis of specialized DNA polymerases expression in human gliomas: association with prognostic significance

Aberrant activation of die translesion DNA synthesis (TLS) pathway has been suggested to play a role in tumorigenesis by promoting genetic mutations. We therefore examined glioma specimens for the expression of specialized DNA polymerases involved in TLS and assessed their prognostic significance. The expression levels of DNA polymerase kappa (Pol kappa), Pol iota, and Pol eta were assessed in 40 primary glioma samples and 10 normal brain samples using quantitative real-time PCR and Western blot analysis. Their prognostic significance was evaluated using a population-based tissue microarray derived from a cohort of 104 glioma patients. Overexpression of Pol kappa and Pol iota was observed in 57.5% (23-40) and 27.5% (11-40) of patients, respectively, whereas no significant expression of Pol eta it was seen in the specimens. Immunohistochemical studies revealed positive Pol kappa and Pol iota staining in 72 (69.2%) and 33 (31.7%) of the 104 glioma specimens, respectively. Pol kappa expression was associated with advanced stages of the disease. Both Pol kappa- and Pol iota- positive staining were associated with shorter survival in glioma patients (P < .001 and P = .014, respectively). A multivariate survival analysis identified Pol kappa as an independent prognostic factor for glioma patients (P < .001). These findings demonstrate, for the first time, that the expression of Pol kappa and Pol iota is deregulated in gliomas, and upregulation of Pol kappa is associated with poorer prognosis in glioma patients.