Modification of DNA damage detecting method, Terminal transferase dependent PCR(TDPCR), and its application to endometrial carcinogenesis

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The involvement of estrogen in endometrial carcinogenesis is controversial、therefore, we intended to examine estrogen or its metabolite could induce DNA damage on endometrial cells by using terminal transferase dependent PCR(TDPCR) method. At first, we modified TDPCR by applying a capillary sequencer and consequently we could avoid its complicated, time-consuming process. By using modified TDPCR, we found that catechol estrogen caused DNA damages on frequently mutated gene in endometrial carcinoma, PTEN, while estrogen did not. In addition, the foci of DNA damage corresponded to known mutation site of PTEN in endometrial carcinoma. Taken together, these data suggest that metabolite of estrogen is responsible for PTEN mutations in endometrial carcinogenesis.