Genomic instability in chronic viral hepatitis and hepatocellular carcinoma.
Chronic hepatitis may progress to cirrhosis and hepatocellular carcinoma (HCC). Progressive accumulation of mutations and genomic instability in chronic viral hepatitis might flag an increased risk of HCC development. Genomic instability at dinucleotide microsatellite loci in chromosomes 2, 13, and 17 and at 2 mononucleotide repeat loci was examined in liver tissues from 41 patients, including 30 without HCC (18 patients with chronic hepatitis and 12 with cirrhosis) and 11 with HCC. Genomic instability was detected in 51% of the 41 cases. Allelic imbalance at informative dinucleotide loci occurred in 37% of the cases. In 14 cases (34%), allelic imbalance was detected in chronic hepatitis or cirrhosis without HCC. Allelic imbalance at the chromosome 13 locus was detected in 50% of the cases of chronic hepatitis C. Allelic imbalance at the TP53 chromosome locus and/or at the chromosome 13 locus was significantly more frequent than alterations at the chromosome 2 locus (P =.026). Low-level microsatellite instability was found in 20% of all cases examined and high-level microsatellite instability in 3 patients (7.5%), including 2 cases of chronic hepatitis and 1 case of cirrhosis. Our results show that allelic imbalance occurs frequently in hepatitis-related HCC as well as in chronic hepatitis in patients without HCC. Allelic imbalance at the D13S170 chromosome 13 locus (13q31.2) occurs frequently in chronic hepatitis, suggesting that genomic alterations affecting the long arm of chromosome 13 might be used to monitor the natural progression of chronic hepatitis-associated liver carcinogenesis.
Dore
M P
MP
Institutes of Internal Medicine, Pathology, and General Surgery, University of Medicine, Sassari, Italy.
Realdi
G
G
Mura
D
D
Onida
A
A
Massarelli
G
G
Dettori
G
G
Graham
D Y
DY
Sepulveda
A R
AR
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000821:virology; D004273:DNA, Neoplasm / Q000032:analysis; D018900:Dinucleotide Repeats; D005260:Female; D005819:Genetic Markers; D019694:Hepatitis B, Chronic / Q000150:complications / Q000235:genetics* / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm; D005819:Genetic Markers