ND4 mutation in transitional cell carcinoma: Does mitochondrial mutation occur before tumorigenesis?
To investigate how mitochondrial mutation occurs in cancers, we analyzed ND4 mutation in 53 transitional cell carcinomas (TCCs) of the upper urinary tract and the normal counterpart (perirenal soft tissue). Three methods, i.e., DNA sequencing, restriction fragment length polymorphism (RFLP), and denaturing high-performance liquid chromatography (DHPLC), were employed because of their different sensitive of detecting mutation. The results of sequencing and RFLP showed that ND4 mutations were only found in 24.5% (13/53) of tumor. However, 11 of these mutations could also be identified in the normal tissue by DHPLC, indicating that most mitochondrial mutations identified in tumors preexist as minor components, which are too low in quantity to be detected by less sensitive methods such as DNA sequencing. The result suggests that mtDNA mutation occurs before tumorigenesis and become apparent in cancer cells.
Tzen
Chin-Yuan
CY
Department of Pathology, Mackay Memorial Hospital, Taipei, Taiwan. jeffrey@ms2.mmh.org.tw
Mau
Bey-Liing
BL
Wu
Tsu-Yen
TY
D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000235:genetics; D001483:Base Sequence; D002295:Carcinoma, Transitional Cell / Q000145:classification / Q000235:genetics* / Q000473:pathology; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009245:NADH Dehydrogenase / Q000235:genetics*; D009711:Nucleotides / Q000235:genetics
D000596:Amino Acids; C098483:NADH dehydrogenase subunit 4; D009711:Nucleotides; D009245:NADH Dehydrogenase