Clonal analysis of precancerous lesion of hepatocellular carcinoma.
OBJECTIVE
It remains to be established whether precancerous lesion (dysplastic nodule) of hepatocellular carcinoma (HCC) is a neoplastic or hyperplastic lesion. Clonal analysis of this lesion was conducted to elucidate this important issue on histogenesis.


METHODS
The method for clonal analysis was based on restriction fragment length polymorphism of the X chromosome-linked phosphoglycerokinase gene and on random inactivation of the gene by methylation. Clonal somatic mutations were also analyzed by DNA fingerprinting with two multilocus probes (33.6 and 33.15), and loss of heterozygosity was studied using five single-locus probes (MS1[1p33-p35], MS31[7p22-pter], MS43a[12q24.3-qter], MS8[5q35-qter], and g3[7q36-qter]).


RESULTS
Clonal analysis by the phosphoglycerokinase gene-based method showed that all of the five dysplastic nodules and seven HCCs were monoclonal in origin. DNA fingerprinting showed clonal somatic mutations in six of 10 dysplastic nodules and in six of nine HCCs. Loss of heterozygosity was found in one dysplastic nodule (7p22-pter) and two HCCs (1p33-p35 and 12q24.3-qter).


CONCLUSIONS
These results confirm monoclonality of HCC and show that hepatic precancerous lesion (dysplastic nodule) is not a hyperplastic but a neoplastic lesion, consisting of monoclonal cells with genetic alterations.
Aihara
T
T
Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.
Noguchi
S
S
Sasaki
Y
Y
Nakano
H
H
Monden
M
M
Imaoka
S
S
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D016172:DNA Fingerprinting; D015342:DNA Probes; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010735:Phosphoglycerate Kinase / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D011230:Precancerous Conditions / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D014960:X Chromosome
D015342:DNA Probes; D010735:Phosphoglycerate Kinase