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

Kim, Hakushi; Komiyama, Tomoyoshi; Inomoto, Chie; Kanazawa, Hiroshi; Kajiwara, Hiroshi; Kobayashi, Hiroyuki; Nakamura, Naoya; Terachi, Toshiro

doi:10.3390/ijms17122049

Cited by 27 publications

(37 citation statements)

References 44 publications

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“…The sampling method for representative cancerous tissues and corresponding noncancerous renal tissues from FFPE tissue specimens was described previously [12]. Briefly, the locations of cancerous tissues and the corresponding noncancerous tissues within the FFPE tissue specimens were recorded by two pathologists (C.I.…”

Section: Rcc Tissue Samplingmentioning

confidence: 99%

“…NC_012920.1 was selected as the reference sequence for the D-loop region. As previously described, the determination of somatic mutations in the D-loop region by comparative sequence analysis was divided into two steps [12]. Initially, we extracted the D-loop sequences of 61 healthy Japanese individuals from DDBJ/EMBL/GenBank databases and then extracted candidates for mutation sites in the D-loop region.…”

Section: Somatic Mutations In the D-loop Regionmentioning

confidence: 99%

“…MT-ND1 sequence data for 61 Japanese patients with localized RCC were extracted from DDBJ/EMBL/GenBank databases, as described in our previous study [12]. Accession numbers were LC178840.1-LC178883.1 and LC178885.1-LC178901.1.…”

Section: Somatic Mutations In the Mt-nd1 Genementioning

confidence: 99%

“…Moreover, several studies have reported that mtDNA mutations may have applications as prognostic markers [10,11]. In a previous study, we analyzed mutations in the mitochondrial NADH dehydrogenase subunit 1 (MT-ND1) gene to determine their associations with clinicopathological parameters and postoperative recurrence of RCC in 62 Japanese patients [12]. Our previous results suggested a significant association between the presence of MT-ND1 mutations and the postoperative recurrence of localized RCC.…”

Section: Introductionmentioning

confidence: 98%

“…Our previous results suggested a significant association between the presence of MT-ND1 mutations and the postoperative recurrence of localized RCC. Accordingly, mtDNA mutations may have applications in predicting malignant behaviors that cannot be explained by clinicopathological findings alone [12,13].…”

Section: Introductionmentioning

confidence: 99%

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D-loop Mutations in Renal Cell Carcinoma Improve Predictive Accuracy for Cancer-Related Death by Integrating with Mutations in the NADH Dehydrogenase Subunit 1 Gene

Kim

Komiyama

Nitta

et al. 2019

Genes

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Renal cell carcinoma (RCC) is associated with various genetic alterations. Although whole-genome/exome sequencing analysis has revealed that nuclear genome alterations are associated with clinical outcomes, the association between nucleotide alterations in the mitochondrial genome and RCC clinical outcomes remains unclear. In this study, we analyzed somatic mutations in the mitochondrial D-loop region, using RCC samples from 61 consecutive patients with localized RCC. Moreover, we analyzed the relationship between D-loop mutations and NADH dehydrogenase subunit 1 (MT-ND1) mutations, which we previously found to be associated with clinical outcomes in localized RCC. Among the 61 localized RCCs, 34 patients (55.7%) had at least one mitochondrial D-loop mutation. The number of D-loop mutations was associated with larger tumor diameter (>32 mm) and higher nuclear grade (≥ISUP grade 3). Moreover, patients with D-loop mutations showed no differences in cancer-specific survival when compared with patients without D-loop mutations. However, the co-occurrence of D-loop and MT-ND1 mutations improved the predictive accuracy of cancer-related deaths among our cohort, increasing the concordance index (C-index) from 0.757 to 0.810. Thus, we found that D-loop mutations are associated with adverse pathological features in localized RCC and may improve predictive accuracy for cancer-specific deaths when combined with MT-ND1 mutations.

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Section: Rcc Tissue Samplingmentioning

confidence: 99%

Section: Somatic Mutations In the D-loop Regionmentioning

confidence: 99%

Section: Somatic Mutations In the Mt-nd1 Genementioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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D-loop Mutations in Renal Cell Carcinoma Improve Predictive Accuracy for Cancer-Related Death by Integrating with Mutations in the NADH Dehydrogenase Subunit 1 Gene

Kim

Komiyama

Nitta

et al. 2019

Genes

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Mitochondrial DNA mutations in ageing and cancer

2022

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Advancing age is a major risk factor for malignant transformation and the development of cancer. As such, over 50% of neoplasms occur in individuals over the age of 70. The pathologies of both ageing and cancer have been characterized by respective groups of molecular hallmarks, and while some features are divergent between the two pathologies, several are shared. Perturbed mitochondrial function is one such common hallmark, and this observation therefore suggests that mitochondrial alterations may be of significance in age-related cancer development. There is now considerable evidence documenting the accumulation of somatic mitochondrial DNA (mtDNA) mutations in ageing human postmitotic and replicative tissues. Similarly, mutations of the mitochondrial genome have been reported in human cancers for decades. The plethora of functions in which mitochondria partake, such as oxidative phosphorylation, redox balance, apoptosis and numerous biosynthetic pathways, manifests a variety of ways in which alterations in mtDNA may contribute to tumour growth. However, the specific mechanisms by which mtDNA mutations contribute to tumour progression remain elusive and often contradictory. This review aims to consolidate current knowledge and describe future direction within the field.

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