1. ¹Department of Paediatrics, Paracelsus Private Medical University Salzburg, Muellner Hauptstr. 48, A-5020 Salzburg, Austria
2. ²Department of Urology, Paracelsus Private Medical University Salzburg, Muellner Hauptstr. 48, A-5020 Salzburg, Austria

Correspondence: Dr B Kofler, E-mail: b.kofler@salk.at

Received 22 August 2005; Revised 22 November 2005; Accepted 29 November 2005; Published online 10 January 2006.

Abstract

Previously, renal cell carcinoma tissues were reported to display a marked reduction of components of the respiratory chain. To elucidate a possible relationship between tumourigenesis and alterations of oxidative phosphorylation, we screened for mutations of the mitochondrial DNA (mtDNA) in renal carcinoma tissues and patient-matched normal kidney cortex. Seven of the 15 samples investigated revealed at least one somatic heteroplasmic mutation as determined by denaturating HPLC analysis (DHPLC). No homoplasmic somatic mutations were observed. Actually, half of the mutations presented a level of heteroplasmy below 25%, which could be easily overlooked by automated sequence analysis. The somatic mutations included four known D-loop mutations, four so far unreported mutations in ribosomal genes, one synonymous change in the ND4 gene and four nonsynonymous base changes in the ND2, COI, ND5 and ND4L genes. One renal cell carcinoma tissue showed a somatic A3243G mutation, which is a known frequent cause of MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episode) and specific compensatory alterations of enzyme activities of the respiratory chain in the tumour tissue. No difference between histopathology and clinical progression compared to the other tumour tissues was observed. In conclusion, the low abundance as well as the frequently observed low level of heteroplasmy of somatic mtDNA mutations indicates that the decreased aerobic energy capacity in tumour tissue seems to be mediated by a general nuclear regulated mechanism.