Mutations of mtDNA in renal cell tumours arising in end-stage renal disease.
Toxic effects in the uraemic state or during maintenance dialysis have been suggested to be responsible for DNA damage and tumour development in end-stage renal disease (ESRD). This study therefore analysed the mitochondrial DNA alterations in six kidneys with ESRD and in nine renal cell tumours arising in these kidneys. Sequencing the entire 16 569 bp mitochondrial genome disclosed 94 sequence variations in normal and corresponding tumour tissues. Thirty-eight polymorphisms occurred in the D-loop region, 40 in the polypeptide coding regions, 12 in the rRNAs, and four in the tRNAs. Nine somatic nucleotide changes were found in seven of the nine tumours analysed; four of them were G to A transitions. Two of the G to A changes occurred in the D-loop region, one in the MTTA gene, and one in the MTND2 gene. An A to G substitution was seen in the control region at the mtTF1 binding site. A T to C transition also occurred also in the D-loop region. A T insertion was seen in MTRNR2 (16S rRNA). One C insertion in MTND4 and one A deletion in the polyA tract of the MTND5 gene resulted in frameshift mutations in two tumours. This study reveals a high mutational rate of the mitochondrial DNA in tumours, which may correspond to the increased level of reactive oxidative species in renal parenchymal cells in ESRD.
Nagy
Anetta
A
Laboratory of Molecular Oncology, Department of Urology, Ruprecht-Karls-University, Heidelberg, Germany.
Wilhelm
Monica
M
Kovacs
Gyula
G
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D004249:DNA Damage / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000235:genetics / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000473:pathology; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods
D004273:DNA, Neoplasm; D012334:RNA, Neoplasm