title: Assessment of differentiation and progression of hepatic tumors using array-based comparative genomic hybridization.
abstract: 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.
authors.affiliation: Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Steinemann
authors.forename: Britta
authors.initials: B
authors.lastname: Skawran
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
authors.forename: Marcel
authors.initials: M
authors.lastname: Tauscher
authors.forename: Anja
authors.initials: A
authors.lastname: Weigmann
authors.forename: Luzie
authors.initials: L
authors.lastname: Wingen
authors.forename: Sarah
authors.initials: S
authors.lastname: Tauscher
authors.forename: Tanja
authors.initials: T
authors.lastname: Hinrichsen
authors.forename: Sabine
authors.initials: S
authors.lastname: Hertz
authors.forename: Peer
authors.initials: P
authors.lastname: Flemming
authors.forename: Jacobus
authors.initials: J
authors.lastname: Flik
authors.forename: Birgit
authors.initials: B
authors.lastname: Wiese
authors.forename: Hans
authors.initials: H
authors.lastname: Kreipe
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Ludwig
authors.initials: L
authors.lastname: Wilkens
mesh_terms: 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
chemical_list: D004273:DNA, Neoplasm