非表示:
キーワード:
oxidative phosphorylation; mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes; denaturing
HPLC; mitochondrial DNA mutations; renal cell carcinoma
要旨:
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.
