title: Genetic profile of hepatocellular carcinoma revealed by array-based comparative genomic hybridization: identification of genetic indicators to predict patient outcome.
abstract: OBJECTIVE
  We conducted an analysis of chromosomal numerical aberrations and their clinical significance in hepatocellular carcinoma.
  
  
  METHODS
  We analyzed 87 hepatocellular carcinomas by array-based comparative genomic hybridization with an array containing 800 bacterial artificial chromosome clones.
  
  
  RESULTS
  Frequent (>30%) chromosomal losses on 1p36.1, 4q21-25, 4q34-35.1, 8p23.3b-11.1, 13q14.1-14.3, 16p13.3, 16q22.1-24.3b, 17p13.3-13.1 and 17p13.3-11, and gains on 1q21-44f, 2q21.2, 2q34, 3q11.2, 5p14.2, 5q13.2-14, 7p22, 7p14.2, 7q21.1, 7q22.3, 7q34, 8q12-24.3 and 17q23, were observed. Recurrent (>5%) amplifications were detected on 1q25, 8q11 and 11q11, and we discovered a novel homozygous deletion at 14q32.11. The extent of chromosomal aberrations correlated significantly with various clinicopathological characteristics of the tumors, and increased in a stepwise manner with the progression of hepatocellular carcinoma. We also identified novel chromosomal alterations that were significantly associated with a range of malignant phenotypes. Multivariate analysis revealed that both chromosomal loss on 17p13.3 and gain on 8q11 are independent prognostic indicators.
  
  
  CONCLUSIONS
  Our results contribute to a complete description of genomic structural aberrations in relation to hepatocarcinogenesis and provide a valuable basis from which we can begin to understand the characteristics of tumors, predict patient outcomes and discover novel therapeutic targets for hepatocellular carcinoma.
authors.affiliation: Pathology Division, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, and Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Katoh
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Shibata
authors.forename: Akiko
authors.initials: A
authors.lastname: Kokubu
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ojima
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Loukopoulos
authors.forename: Yae
authors.initials: Y
authors.lastname: Kanai
authors.forename: Tomoo
authors.initials: T
authors.lastname: Kosuge
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Michiie
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Fumie
authors.initials: F
authors.lastname: Hosoda
authors.forename: Misao
authors.initials: M
authors.lastname: Ohki
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.forename: Setsuo
authors.initials: S
authors.lastname: Hirohashi
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D002877:Chromosomes, Human; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011379:Prognosis; D015203:Reproducibility of Results; D012189:Retrospective Studies; D015996:Survival Rate