RNA-seq and Mitochondrial DNA Analysis of Adrenal Gland Metastatic Tissue in a Patient with Renal Cell Carcinoma

Abstract

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 (ND1) 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.

Therapeutic options for different metastatic sites arising from renal cell carcinoma: A review

“…Patients with RCC may develop metastatic disease at various anatomical sites. Synthesizing evidence from several researches conducted by Chatzizacharias NA et al, Komiyama T et al, Dudani S et al, and a study of IMDC, [49][50][51][52] we suggest that despite disparities in research outcomes regarding the common sites for RCC metastasis and discrepancies in the incidence of metastasis to different organs among distinct subtypes of RCC (Clear Cell RCC [ccRCC], papillary RCC, and chromophobe RCC), the predominant sites of metastasis can be delineated as follows: lungs, lymph nodes (LNs), bones, liver, brain, and adrenal glands. Notably, Gen'an Longren et al found that the therapeutic efficacy in mRCC may diverge contingent upon the specific organ site of metastasis.…”