Significant existence of deleted mitochondrial DNA in cirrhotic liver surrounding hepatic tumor.
To understand the role of mitochondria in carcinogenesis, we compared the amount of deleted mtDNAs between human hepatic tumors and surrounding cirrhotic portion of the liver of ten patients by using polymerase chain reaction (PCR). Multiple mtDNA deletions were detected in cirrhotic portion, but no deletions were detected in the tumor portion. Direct sequencing of the fragments revealed a 7,079-bp deletion (nucleotide position 8,992-16,072) involving no direct repeated sequences and a 7,436-bp deletion (position 8,649-16,084) involving a 12-bp directly repeated sequence of 5'-CATCAACAACCG-3' exists in both the ATP6 gene and the D-loop region. These mtDNA mutations could be one of the endogenous factors that induce somatic mutations in nuclear genome and etiologically contribute to human carcinogenesis.
Yamamoto
H
H
First Department of Surgery, Faculty of Medicine, University of Nagoya, Japan.
Tanaka
M
M
Katayama
M
M
Obayashi
T
T
Nimura
Y
Y
Ozawa
T
T
D002759:Adenoma, Bile Duct / Q000150:complications / Q000235:genetics*; D000328:Adult; D000368:Aged; D001482:Base Composition; D001483:Base Sequence; D015139:Blotting, Southern; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics*; D002872:Chromosome Deletion; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics*; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics*; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D012091:Repetitive Sequences, Nucleic Acid
D004272:DNA, Mitochondrial; D009838:Oligodeoxyribonucleotides