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

60 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
Pages (from-to)863-874
Number of pages12
JournalJournal of Hepatology
Volume43
Issue number5
DOIs
Publication statusPublished - 2005 Nov

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Comparative Genomic Hybridization
Hepatocellular Carcinoma
Chromosome Aberrations
Bacterial Artificial Chromosomes
Neoplasms
Multivariate Analysis
Clone Cells
Phenotype
Therapeutics

Keywords

  • Array-based comparative genomic hybridization
  • Hepatocellular carcinoma
  • Multistep carcinogenesis
  • Multivariate analysis
  • Prognosis

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Genetic profile of hepatocellular carcinoma revealed by array-based comparative genomic hybridization : Identification of genetic indicators to predict patient outcome. / Katoh, Hiroto; Shibata, Tatsuhiro; Kokubu, Akiko; Ojima, Hidenori; Loukopoulos, Panayiotis; Kanai, Yae; Kosuge, Tomoo; Fukayama, Masashi; Kondo, Tadashi; Sakamoto, Michiie; Hosoda, Fumie; Ohki, Misao; Imoto, Issei; Inazawa, Johji; Hirohashi, Setsuo.

In: Journal of Hepatology, Vol. 43, No. 5, 11.2005, p. 863-874.

Research output: Contribution to journalArticle

Katoh, H, Shibata, T, Kokubu, A, Ojima, H, Loukopoulos, P, Kanai, Y, Kosuge, T, Fukayama, M, Kondo, T, Sakamoto, M, Hosoda, F, Ohki, M, Imoto, I, Inazawa, J & Hirohashi, S 2005, 'Genetic profile of hepatocellular carcinoma revealed by array-based comparative genomic hybridization: Identification of genetic indicators to predict patient outcome', Journal of Hepatology, vol. 43, no. 5, pp. 863-874. https://doi.org/10.1016/j.jhep.2005.05.033
Katoh, Hiroto ; Shibata, Tatsuhiro ; Kokubu, Akiko ; Ojima, Hidenori ; Loukopoulos, Panayiotis ; Kanai, Yae ; Kosuge, Tomoo ; Fukayama, Masashi ; Kondo, Tadashi ; Sakamoto, Michiie ; Hosoda, Fumie ; Ohki, Misao ; Imoto, Issei ; Inazawa, Johji ; Hirohashi, Setsuo. / Genetic profile of hepatocellular carcinoma revealed by array-based comparative genomic hybridization : Identification of genetic indicators to predict patient outcome. In: Journal of Hepatology. 2005 ; Vol. 43, No. 5. pp. 863-874.
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T2 - Identification of genetic indicators to predict patient outcome

AU - Katoh, Hiroto

AU - Shibata, Tatsuhiro

AU - Kokubu, Akiko

AU - Ojima, Hidenori

AU - Loukopoulos, Panayiotis

AU - Kanai, Yae

AU - Kosuge, Tomoo

AU - Fukayama, Masashi

AU - Kondo, Tadashi

AU - Sakamoto, Michiie

AU - Hosoda, Fumie

AU - Ohki, Misao

AU - Imoto, Issei

AU - Inazawa, Johji

AU - Hirohashi, Setsuo

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N2 - 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.

AB - 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.

KW - Array-based comparative genomic hybridization

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KW - Multistep carcinogenesis

KW - Multivariate analysis

KW - Prognosis

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