Mitochondrial Alterations in Solid Carcinomas
Relationship between Tumorgenesis of Human Kidney Carcinomas and Mitochondrial DNA (mtDNA) Alterations
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Alterations of the respiratory chain and mutations of the mitochondrial DNA (mtDNA) have been extensively investigated in a wide variety of neoplasias. However, no obvious correlation of a certain type of tumor and mtDNA mutations has been reported so far. I compared both, enzymatic measurements of the respiratory chain and mtDNA mutations in renal carcinomas and renal oncocytomas. To enable a high throughput screen of mtDNA variations, I developed a DHPLC-based protocol for a rapid detection of unknown variations of the entire human mtDNA. The benign renal oncocytomas were in clear contrast t...
Alterations of the respiratory chain and mutations of the mitochondrial DNA (mtDNA) have been extensively investigated in a wide variety of neoplasias. However, no obvious correlation of a certain type of tumor and mtDNA mutations has been reported so far. I compared both, enzymatic measurements of the respiratory chain and mtDNA mutations in renal carcinomas and renal oncocytomas. To enable a high throughput screen of mtDNA variations, I developed a DHPLC-based protocol for a rapid detection of unknown variations of the entire human mtDNA. The benign renal oncocytomas were in clear contrast to the malign renal carcinomas. The oncocytomas showed significantly increased Krebs cycle- and OXPHOS enzyme activities, except a total breakdown of the complex I enzyme activity. The mutation screening revealed frame shift mutations, encoding mitochondrial ND genes in 8 out of 12 oncocytomas. All these somatic frame shift mutations displayed a homoplasmy of 100%. This study shows for the first time a direct correlation of mtDNA mutations in a specific type of cancer, which leads to a total lack of complex I enzyme activity in the respiratory chain.
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