Komiyama Tomoyoshi, Kim Hakushi, Tanaka Masayuki, Isaki Sanae, Yokoyama Keiko, Miyajima Akira, Kobayashi Hiroyuki
Department of Clinical Pharmacology, Tokai University School of Medicine, Kanagawa, Isehara 259-1193, Japan.
Department of Urology, Tokai University Hachioji Hospital, Tokyo 192-0032, Japan.
Biology (Basel). 2022 Apr 13;11(4):589. doi: 10.3390/biology11040589.
This study aimed to clarify whether genetic mutations participate in renal cell carcinoma (RCC) metastasis to the adrenal gland (AG). Our study analyzed whole mitochondrial gene and ribonucleic acid sequencing (RNA-seq) data from a male patient in his 60s with metastatic RCC. We confirmed common mutation sites in the mitochondrial gene and carried out Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using RNA-seq data for RCC and adrenal carcinoma. Furthermore, we confirmed the common mutation sites of mitochondrial genes in which the T3394Y (p.H30Y) site transitioned from histidine (His.; H) to tyrosine (Tyr.; Y) in the NADH dehydrogenase subunit 1 () gene. The R11,807G (p.T350A) site transitioned from threonine (Thr.; T) to alanine (Ala.; A). Additionally, the G15,438R or A (p.G231D) site transitioned from glycine (Gly.; G) to aspartic acid (Asp.; D) in cytochrome b (CYTB). Furthermore, pathway analysis, using RNA-seq, confirmed the common mutant pathway between RCC and adrenal carcinoma as cytokine-cytokine receptor (CCR) interaction. Confirmation of the original mutation sites suggests that transfer to AG may be related to the CCR interaction. Thus, during metastasis to the AG, mitochondria DNA mutation may represent the initial origin of the metastasis, followed by the likely mutation of the nuclear genes.
本研究旨在阐明基因突变是否参与肾细胞癌（RCC）转移至肾上腺（AG）的过程。我们的研究分析了一名60多岁男性转移性肾细胞癌患者的全线粒体基因和核糖核酸测序（RNA-seq）数据。我们确定了线粒体基因中的常见突变位点，并利用肾细胞癌和肾上腺癌的RNA-seq数据进行了京都基因与基因组百科全书（KEGG）分析。此外，我们确定了线粒体基因的常见突变位点，其中NADH脱氢酶亚基1（）基因中的T3394Y（p.H30Y）位点从组氨酸（His.；H）转变为酪氨酸（Tyr.；Y）。R11,807G（p.T350A）位点从苏氨酸（Thr.；T）转变为丙氨酸（Ala.；A）。此外，细胞色素b（CYTB）中的G15,438R或A（p.G231D）位点从甘氨酸（Gly.；G）转变为天冬氨酸（Asp.；D）。此外，利用RNA-seq进行的通路分析证实了肾细胞癌和肾上腺癌之间的常见突变通路为细胞因子-细胞因子受体（CCR）相互作用。对原始突变位点的确认表明，转移至肾上腺可能与CCR相互作用有关。因此，在转移至肾上腺的过程中，线粒体DNA突变可能代表转移的初始起源，随后可能是核基因的突变。
