Genetic profile of hepatocellular carcinoma revealed by array-based comparative genomic hybridization: identification of genetic indicators to predict patient outcome.
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.
Katoh
Hiroto
H
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.
Shibata
Tatsuhiro
T
Kokubu
Akiko
A
Ojima
Hidenori
H
Loukopoulos
Panayiotis
P
Kanai
Yae
Y
Kosuge
Tomoo
T
Fukayama
Masashi
M
Kondo
Tadashi
T
Sakamoto
Michiie
M
Hosoda
Fumie
F
Ohki
Misao
M
Imoto
Issei
I
Inazawa
Johji
J
Hirohashi
Setsuo
S
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