Assessment of differentiation and progression of hepatic tumors using array-based comparative genomic hybridization.
OBJECTIVE
To gain more information about the molecular mechanisms leading to dedifferentiation of hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC), high-resolution array-based comparative genomic hybridization (array-CGH) was performed on 24 cases of HCC and 10 cases of HCA.


METHODS
DNA chips containing 6251 individual bacterial artificial chromosome/plasmid artificial chromosome clones were used. They allowed for a genome-wide resolution of 1 Mb and an even higher resolution of up to 100 kb for chromosome regions recurrently involved in human tumors and for regions containing known tumor-suppressor genes and oncogenes.


RESULTS
Copy number changes on the genomic scale were found by array-based comparative genomic hybridization in all cases. In HCC, gains of chromosomal regions 1q (91.6%), and 8q (58.3%), and losses of 8p (54%) were found most frequently. Hierarchic cluster analysis branched all HCA from HCC. However, in 2 adenomas with a known history of glycogenosis type I and adenomatosis hepatis gains of 1q were found, too. The critically gained region was narrowed down to bands 1q22-23. Although no significant differences in the mean number of chromosomal aberrations were seen between adenomas and well-differentiated carcinomas (2.7 vs 4.6), a significant increase accompanied the dedifferentiation of HCC (14.1 in HCC-G2 and 16.3 in HCC-G2/3; P < .02). Dedifferentiation of HCC also was correlated closely to losses of 4q and 13q (P <.001 and <.005, respectively).


CONCLUSIONS
The increased chromosomal instability during dedifferentiation of HCC leads to an accumulation of structural chromosomal aberrations and losses and gains of defined chromosome regions.
Steinemann
Doris
D
Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany.
Skawran
Britta
B
Becker
Thomas
T
Tauscher
Marcel
M
Weigmann
Anja
A
Wingen
Luzie
L
Tauscher
Sarah
S
Hinrichsen
Tanja
T
Hertz
Sabine
S
Flemming
Peer
P
Flik
Jacobus
J
Wiese
Birgit
B
Kreipe
Hans
H
Lichter
Peter
P
Schlegelberger
Brigitte
B
Wilkens
Ludwig
L
D018248:Adenoma, Liver Cell / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002648:Child; D016000:Cluster Analysis; D004273:DNA, Neoplasm / Q000032:analysis*; D003937:Diagnosis, Differential; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis
D004273:DNA, Neoplasm