Multiple chromosomal abnormalities in human liver (pre)neoplasia.
OBJECTIVE
In human hepatocarcinogenesis the tumor precursor lesions and the sequence of genetic aberrations are not known. We therefore compared genetic alterations of different types of benign liver lesions to those of hepatocellular carcinoma.


METHODS
By comparative genomic hybridisation (CGH) 40 cases, including cirrhotic liver (CL), focal nodular hyperplasia (FNHs), hepatocellular adenoma (HCAs), dysplastic nodules (DNs), primary hepatocellular carcinoma (HCCs), and hepatocellular metastases to the lung were studied.


RESULTS
FNHs and HCAs exhibited few chromosomal abnormalities. Frequency and pattern of genetic alterations in DNs highly resembled those in HCCs: gains of DNA clustered in chromosome arms 1p/q, 7q, 15q, 16p, 17q, and 20q and losses were often found at 3p, 4q, 9p, and 11q. Aberrations on 1p, 6q, 8p/q, and 13q occurred almost exclusively in HCCs; the gain at 8q encompassed amplification of c-myc, as verified by fluorescence in situ hybridisation.


CONCLUSIONS
The pattern of genetic alterations in HCCs resembled more the alterations found in DNs than in FNHs and HCAs, suggesting that DNs may be the actual tumor precursors. Furthermore, alterations at 4q, 9p, 11q, 16p, and 17q appear as early genetic events being crucial for hepatocarcinogenesis.
Raidl
Maria
M
Institute of Cancer Research, University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
Pirker
Christine
C
Schulte-Hermann
Rolf
R
Aubele
Michaela
M
Kandioler-Eckersberger
Daniela
D
Wrba
Fritz
F
Micksche
Michael
M
Berger
Walter
W
Grasl-Kraupp
Bettina
B
D018248:Adenoma, Liver Cell / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics*; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D016259:Genes, myc; D006801:Humans; D006965:Hyperplasia; D017404:In Situ Hybridization, Fluorescence; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics*
D004273:DNA, Neoplasm