MP72-20 SOMATIC MUTATIONS IN MITOCHONDRIAL DNA PREDICT POSTOPERATIVE RECURRENCE IN RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology II1 Apr 2018MP72-20 SOMATIC MUTATIONS IN MITOCHONDRIAL DNA PREDICT POSTOPERATIVE RECURRENCE IN RENAL CELL CARCINOMA Hakushi Kim, Tomoyoshi Komiyama, Takato Uchida, Tatsuo Kano, Souichiro Yuzuriha, Tatsuya Ootaki, Tatsuya Umemoto, Yuki Shimizu, Masayoshi Kawakami, Nobuyuki Nakajima, Masahiro Nitta, Kazuya Hanai, Yoshiaki Kawamura, Hiroshi Kamiguchi, Chie Inomoto, Hiroshi Kajiwara, Naoya Nakamura, Hiroyuki Kobayashi, and Akira Miyajima Hakushi KimHakushi Kim More articles by this author , Tomoyoshi KomiyamaTomoyoshi Komiyama More articles by this author , Takato UchidaTakato Uchida More articles by this author , Tatsuo KanoTatsuo Kano More articles by this author , Souichiro YuzurihaSouichiro Yuzuriha More articles by this author , Tatsuya OotakiTatsuya Ootaki More articles by this author , Tatsuya UmemotoTatsuya Umemoto More articles by this author , Yuki ShimizuYuki Shimizu More articles by this author , Masayoshi KawakamiMasayoshi Kawakami More articles by this author , Nobuyuki NakajimaNobuyuki Nakajima More articles by this author , Masahiro NittaMasahiro Nitta More articles by this author , Kazuya HanaiKazuya Hanai More articles by this author , Yoshiaki KawamuraYoshiaki Kawamura More articles by this author , Hiroshi KamiguchiHiroshi Kamiguchi More articles by this author , Chie InomotoChie Inomoto More articles by this author , Hiroshi KajiwaraHiroshi Kajiwara More articles by this author , Naoya NakamuraNaoya Nakamura More articles by this author , Hiroyuki KobayashiHiroyuki Kobayashi More articles by this author , and Akira MiyajimaAkira Miyajima More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2304AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Mitochondrial DNA (mtDNA) accumulates mutations at a 10-fold higher rate than nuclear DNA, owing to the lack of protective histones and limited capacity for DNA repair. It contains 13 coding genes involved in oxidative phosphorylation and a non-coding region, which includes a displacement loop (D-loop), regulating mtDNA replication. To examine the correlation between mtDNA mutations and postoperative recurrence in RCC, we focused on mutations in ND1, encoding NADH dehydrogenase subunit 1, as a coding gene representative and D-loop as a non-coding region representative. METHODS Clinicopathological data were collected from a total of 61 patients, who underwent radical surgery for localized RCC in 2010. The sequences of ND1 and D-loop (mtDNA) in RCC tissues were compared with the sequence data from corresponding non-cancerous renal tissues. Clinicopathological features included age, sex, histological subtype, pathological stage T (pT), nuclear grade, microvascular invasion (MVI), and mtDNA mutations. The associations of clinicopathological features with time to postoperative recurrence after curative surgery were evaluated by statistical analysis. RESULTS Among the 61 patients, there were 47 male and 14 female patients with a median age of 62 (39-80) years. The median follow-up period was 66.5 (29-76) months. Of the 61 patients, 10 had recurrent RCC. Concerning pathological characteristics, there were 54 patients with clear cell RCC and 7 patients with non-clear cell RCC. Fifty-six patients had pT 1-2 tumors, and the others had pT 3-4 tumors. Fuhrman grading showed that 53 cases were grade I/II, and 8 cases were grade III/IV. MVI was observed in 13 patients. Among the 61 RCC cases, mtDNA gene sequencing revealed the existence of somatic mutations in 14 cases. The 5-year RFS rate was significantly low in patients with pT stage ≥ 3, Fuhrman grade ≥ III, MVI, and mtDNA gene mutations (Figure). Multivariate analysis using these factors showed that mtDNA gene mutations constituted an independent risk factor for postoperative recurrence after curative surgery. CONCLUSIONS This is the first study to demonstrate a relationship between mtDNA mutations and postoperative recurrence in RCC. Mutations in the mitochondrial ND1 and D-loop may be useful biomarkers for the detection of postoperative recurrence in RCC. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e960 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Hakushi Kim More articles by this author Tomoyoshi Komiyama More articles by this author Takato Uchida More articles by this author Tatsuo Kano More articles by this author Souichiro Yuzuriha More articles by this author Tatsuya Ootaki More articles by this author Tatsuya Umemoto More articles by this author Yuki Shimizu More articles by this author Masayoshi Kawakami More articles by this author Nobuyuki Nakajima More articles by this author Masahiro Nitta More articles by this author Kazuya Hanai More articles by this author Yoshiaki Kawamura More articles by this author Hiroshi Kamiguchi More articles by this author Chie Inomoto More articles by this author Hiroshi Kajiwara More articles by this author Naoya Nakamura More articles by this author Hiroyuki Kobayashi More articles by this author Akira Miyajima More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...