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, Masafumi; Imoto, Issei; Inazawa, Johji; Hirohashi, Setsuo

doi:10.1016/j.jhep.2005.05.033

Cited by 65 publications

(49 citation statements)

References 56 publications

(78 reference statements)

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“…Our results indicated that GIM can detect the allelic status more accurately than methods used previously (Kusano et al, 1999;Niketeghad et al, 2001). For example, several HCC samples analysed in the present study had UPD or UPT, which may be missed or recognized as gain regions by CGH, as both CGH and array-based CGH can only detect total copy changes (Hashimoto et al, 2004;Katoh et al, 2005;Patil et al, 2005). Uniparental disomy or UPT are exceptional derivations of a pair of offspring chromosomes from one parent only (Engel, 1980) and cause an increased risk of recessive disorders, such as Wiedemann-Beckwith (Henry et al, 1991), Prader-Willi (Nicholls et al, 1989) and Angelman syndromes (Malcolm et al, 1991) owing to reduction to homozygosity (Engel, 1993).…”

Section: Discussionmentioning

confidence: 53%

Molecular karyotyping of human hepatocellular carcinoma using single-nucleotide polymorphism arrays

et al. 2006

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Section: Discussionmentioning

confidence: 53%

Molecular karyotyping of human hepatocellular carcinoma using single-nucleotide polymorphism arrays

et al. 2006

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“…Sixteen-bit fluorescence intensity TIF images were obtained using a scanner (FLA8000, Fuji Film, Tokyo, Japan) and analyzed using GenePix Pro 5.0 (Axon Instruments, Inc., Foster City, CA). Thresholds for chromosomal gain (ratio >1.25) and loss (ratio <0.75) were determined by ''normal versus normal experiments'' (23,24). We also validated our array CGH data by other methods.…”

Section: Methodsmentioning

confidence: 95%

“…Loss of the 17p13 locus was confirmed by loss of heterozygosity of the p53 gene, which is located within that bacterial artificial chromosome using a microsatellite marker (TP53CA). Gene amplification of a representative gene, cyclin D1, was validated by fluorescence in situ hybridization analysis (24). We applied multiplex ligation-dependent probe amplification (MLPA) to validate ourarray data.…”

Section: Methodsmentioning

confidence: 99%

Genetic Classification of Lung Adenocarcinoma Based on Array-Based Comparative Genomic Hybridization Analysis: Its Association with Clinicopathologic Features

Shibata¹,

Uryu

Kokubu³

et al. 2005

Clinical Cancer Research

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The array-based comparative genomic hybridization using microarrayed bacterial artificial chromosome clones allows high-resolution analysis of genome-wide copy number changes in tumors. To analyze the genetic alterations of primary lung adenocarcinoma in a high-throughput way, we used laser-capture microdissection of cancer cells and array comparative genomic hybridization focusing on 800 chromosomal loci containing cancer-related genes.We identified a large number of chromosomal numerical alterations, including frequent amplifications on 7p12, 11q13,12q14-15, and 17q21, and two homozygous deletions on 9p21 and one on 8p23. Unsupervised hierarchical clustering analysis of multiple alterations revealed three subgroups of lung adenocarcinoma that were characterized by the accumulation of distinct genetic alterations and associated with smoking history and gender. The mutation status of the epidermal growth factor receptor (EGFR) gene was significantly associated with specific genetic alterations and supervised clustering analysis based on EGFR gene mutations elucidated a subgroup including all EGFR gene mutated tumors, which showed significantly shorter disease-free survival. Our results suggest that there exist multiple molecular carcinogenesis pathways in lung adenocarcinoma that may associate with smoking habits and gender, and that genetic cancer profiling will reveal previously uncharacterized genetic heterogeneity of cancer and be beneficial in estimating patient prognosis and discovering novel cancer-related genes including therapeutic targets.

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“…22 In that study, all of the 60 HCC tumors analyzed in this study were also investigated and the chromosomal alteration profiles of these 60 HCCs have been clearly defined. Details of procedures of aCGH analysis have been previously described.…”

Section: Array-based Comparative Genomic Hybridization (Acgh) Analysimentioning

confidence: 99%

“…Details of procedures of aCGH analysis have been previously described. [22][23][24] We determined thresholds for chromosomal gain (ratio Ͼ1.25) and loss (ratio Ͻ0.75) by repeatedly performed normal versus normal control experiments. 22,23,25 …”

Section: Array-based Comparative Genomic Hybridization (Acgh) Analysimentioning

confidence: 99%

Epigenetic Instability and Chromosomal Instability in Hepatocellular Carcinoma

Katoh

Shibata

Kokubu

et al. 2006

The American Journal of Pathology

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The aim of this study was to clarify the association between the epigenetic instability phenotype and the chromosomal instability phenotype in primary hepatocellular carcinoma (HCC). Sixty primary HCC tumors were examined. Methylation status for nine CpG islands (the p16, COX2, GSTP1, RASSF1A, E-cadherin, and APC gene promoters, and the MINT 1, 25, and 31 clones) was evaluated by methylation-specific polymerase chain reaction. Chromosomal structural alterations of these 60 HCC tumors were characterized in our previous study by using whole genomic arraybased comparative genomic hybridization. We found that the epigenetic instability phenotype and the chromosomal instability phenotype are not mutually exclusive in hepatocarcinogenesis and that they do not show a simple cause-and-effect relationship. Hepatitis virus infection in the background liver was significantly associated with these instability phenotypes. Furthermore, we identified an epigenetic instability-dependent HCC that shows frequent epigenetic aberrations without chromosomal instability. It was noteworthy that epigenetic instability-positive and -negative HCCs displayed distinctive combinations of chromosomal structural alterations. In summary, by combined analyses of genetic and epigenetic aberration profiles in HCC, we obtained a comprehensive view of genomic alterations in hepatocarcinogenesis. Our results have clinical relevance because epigenetic instability-dependent HCCs may respond well to methylation inhibitory therapies. (Am J Pathol

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

Cited by 65 publications

References 56 publications

Molecular karyotyping of human hepatocellular carcinoma using single-nucleotide polymorphism arrays

Molecular karyotyping of human hepatocellular carcinoma using single-nucleotide polymorphism arrays

Genetic Classification of Lung Adenocarcinoma Based on Array-Based Comparative Genomic Hybridization Analysis: Its Association with Clinicopathologic Features

Epigenetic Instability and Chromosomal Instability in Hepatocellular Carcinoma

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