Somatic mutations in pol β, pol η and pol κ genes in prostate cancer

Abstract

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Error prone (EP) DNA repair (also called translesion synthesis) involves DNA polymerases that are much more accurate when replicating through specific types of DNA damage than undamaged DNA (such as pol η and pol κ). EP DNA polymerases have been proposed to play a role in cancer etiology. Somatic mutations of the base excision repair (BER) specific DNA polymerase pol β have been found in a variety of cancers. We sequenced the coding regions of the pol β, pol η, and pol κ genes in 26 prostate cancer patients. We identified 27 somatic mutations in these genes, 14 of which were missense substitutions, 9 were silent or intronic substitutions, two substitutions changed splice acceptor (AG) sites, one was in the promoter region and one in the 5’-UTR. One intronic substitution was recurrent. One missense substitution was also present in the corresponding patient’s genomic DNA and hence was probably a constitutional (“germline”) DNA polymorphism. Overall, among 26 patients analyzed, 19 patients (73%) have somatic mutations in a polymerase gene and 16 patients (61%) have somatic mutations in pol β. Some of these mutations affect fidelity of DNA synthesis while others are in pol η codons causing Xeroderma Pigmentosum Variant (XPV). We propose that EP and BER polymerase gene mutations are associated with prostate cancer progression.