Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0162671 (MELAS)
 587 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal cell carcinoma (RCC) is a rare pediatric renal cancer. Recent molecular genetic studies discovered a tumor-specific mutation involving translocation of a transcription factor TFE3 in a subset of pediatric RCC with distinct histopathology. We reported a case of a 2-year-old boy with RCC associated with TFE3 translocation resulting in a PRCC-TFE3 fusion gene. Interestingly, the case carried a maternally inherited mitochondrial DNA (mtDNA) alteration at the position which is usually found in MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes) syndrome (A3243G). Although evidence of somatic alterations in mtDNA existed in various cancers, association between inherited mtDNA mutation and pediatric renal cancer has not been reported. Our case provided the first evidence of a co-occurrence between a germ line mutation in mtDNA and the somatic mutation of pediatric RCC. With this information, we speculated a role of mitochondria mutation in the pathogenesis of this cancer.
 ...
PMID:Renal cell carcinoma in a pediatric patient with an inherited mitochondrial mutation. 1601 May 49

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.
 ...
PMID:Mitochondrial DNA mutations in renal cell carcinomas revealed no general impact on energy metabolism. 1640 28