@article{oai:repo.qst.go.jp:00049614, author = {Nuryadi, Endang and Sasaki, Yasushi and Hagiwara, Yoshihiko and Bunga Mayang Permata, Tiara and Sato, Hiro and Komatsu, Shuichiro and Yoshimoto, Yuya and Murata, Kazutoshi and Ando, Ken and Kubo, Nobuteru and Okonogi, Noriyuki and Takakusagi, Yosuke and Adachi, Akiko and Iwanaga, Mototaro and Tsuchida, Keisuke and Tamaki, Tomoaki and Shin-Ei, Noda and Hirota, Yuka and Shibata, Atsushi and Ohno, Tatsuya and Tokino, Takashi and Oike, Takahiro and Nakano, Takashi and Yoshimoto, Yuya and Murata, Kazutoshi and Ando, Ken and Kubo, Nobuteru and Okonogi, Noriyuki and Tamaki, Tomoaki and Shibata, Atsushi and Ohno, Tatsuya and Nakano, Takashi}, issue = {66}, journal = {Oncotarget}, month = {Aug}, note = {Radiotherapy is an essential component of cancer therapy. Despite advances in cancer genomics, the mutation signatures of radioresistant tumors have not yet been fully elucidated. To address this issue, we analyzed a unique set of clinical specimens from a uterine cervical cancer that repeatedly locally recurred after multiple rounds of radiotherapy. Exon sequencing of 409 cancer-related genes in the treatment-naïve tumor and the tumors that recurred after initial and secondary radiotherapy identified (i) activating mutations in and , and putative inactivating mutations in , as trunk mutation signatures that persisted over the clinical course; and (ii) mutations in , , and as acquired mutation signatures observed only in recurrent tumors after radiotherapy. Comprehensive mining of published genomics data pertaining to radiosensitivity revealed that simultaneous mutations in and , which have not been described previously in uterine cervical cancer, are associated with cancer cell radioresistance. The association between this mutation signature and radioresistance was validated by isogenic cell-based experiments. These results provide proof-of-principle for the analytical pipeline employed in this study, which explores clinically relevant mutation signatures for radioresistance, and demonstrate that this approach is worth pursuing with larger cohorts in the future.}, pages = {32642--32652}, title = {Mutational analysis of uterine cervical cancer that survived multiple rounds of radiotherapy.}, volume = {9}, year = {2018} }