Novel mitochondrial DNA deletion found in a renal cell carcinoma

Polymerase chain reaction (PCR) was used to analyze a rarely deleted region of mitochondrial DNA (mtDNA) from 39 human renal cell carcinomas (RCC) and matched normal kidney tissue removed during radical nephrectomy. One tumor specimen (E.R.) had a unique PCR product approximately 250 base pairs (bp) smaller than the PCR product found in the normal E.R. kidney. Sequence analysis of the tumor-specific PCR fragment revealed a 264 bp deletion in the first subunit (NDI) of NADH:ubiquinone oxidoreductase (complex I) of the electron transport chain. Southern analysis of the RCCs demonstrated that approximately 50% of the mtDNA molecules in the primary RCC contained a unique 3.2 kb EcoRV restriction fragment found only in E.R. tumor mtDNA. Northern analysis demonstrated preferential transcription of the truncated NDI mRNA. None of the five metastases or any normal tissue from E.R. contained levels of the NDI deletion detectable by PCR. This is the first reported case of an intragenic NDI mtDNA deletion.