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Int. J. Mol. Sci. 2016, 17(12), 2049; doi:10.3390/ijms17122049

Mutations in the Mitochondrial ND1 Gene Are Associated with Postoperative Prognosis of Localized Renal Cell Carcinoma

1
Department of Urology, Tokai University School of Medicine, Kanagawa, Isehara 259-1193, Japan
2
Department of Clinical Pharmacology, Tokai University School of Medicine, Kanagawa, Isehara 259-1193, Japan
3
Department of Pathology, Tokai University School of Medicine, Kanagawa, Isehara 259-1193, Japan
4
Support Center for Medical Research and Education, Tokai University, Kanagawa, Isehara 259-1193, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 26 October 2016 / Revised: 28 November 2016 / Accepted: 29 November 2016 / Published: 7 December 2016
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

We analyzed mutations in the mitochondrial ND1 gene to determine their association with clinicopathological parameters and postoperative recurrence of renal cell carcinoma (RCC) in Japanese patients. Among 62 RCC cases for which tumor pathology was confirmed by histopathology, ND1 sequencing revealed the presence of 30 mutation sites in 19 cases. Most mutations were heteroplasmic, with 16 of 19 cases harboring one or more heteroplasmic sites. Additionally, 12 sites had amino acid mutations, which were frequent in 10 of the cases. The 5-year recurrence-free survival (RFS) rate was significantly worse in patients with tumors >40 mm in diameter (p = 0.0091), pathological T (pT) stage ≥3 (p = 0.0122), Fuhrman nuclear atypia grade ≥III (p = 0.0070), and ND1 mutations (p = 0.0006). Multivariate analysis using these factors revealed that mutations in ND1 were significantly associated with the 5-year RFS rate (p = 0.0044). These results suggest a strong correlation between the presence of ND1 mutations in cancer tissue and postoperative recurrence of localized RCC in Japanese patients. View Full-Text
Keywords: mitochondrial DNA; ND1; renal cell carcinoma; prognostic factor; polymorphism; heteroplasmy; nucleotide differentiation index mitochondrial DNA; ND1; renal cell carcinoma; prognostic factor; polymorphism; heteroplasmy; nucleotide differentiation index
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Kim, H.; Komiyama, T.; Inomoto, C.; Kamiguchi, H.; Kajiwara, H.; Kobayashi, H.; Nakamura, N.; Terachi, T. Mutations in the Mitochondrial ND1 Gene Are Associated with Postoperative Prognosis of Localized Renal Cell Carcinoma. Int. J. Mol. Sci. 2016, 17, 2049.

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