Genetic profile of hepatocellular carcinoma revealed by array-based comparative genomic hybridization: identification of genetic indicators to predict patient outcome.

Hiroto Katoh, Tatsuhiro Shibata, Akiko Kokubu, Hidenori Ojima, Panayiotis Loukopoulos, Yae Kanai, Tomoo Kosuge, Masashi Fukayama, Tadashi Kondo, Michiie Sakamoto, Fumie Hosoda, Misao Ohki, Issei Imoto, Johji Inazawa, Setsuo Hirohashi

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

BACKGROUND/AIMS: 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.
Original languageEnglish
Article number16139920
Pages (from-to)863-74
Number of pages12
JournalJournal of Hepatology
Volume43
Issue number5
Publication statusPublished - Nov 2005

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