Deletion mapping of chromosome 16q in hepatocellular carcinoma

Piao, Zhe; Park, C; Kim, J J; Kim, Hyunkyu

doi:10.1038/sj.bjc.6690431

Cited by 30 publications

(24 citation statements)

References 16 publications

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“…2,3,12,13 Loss of 16q was also frequently detected in other solid tumors including breast, 14 lung, 15 and gastric cancers, 16 suggesting that 16q may harbor one or more TSGs and its inactivation plays a key role in the pathogenesis of many malignancies including HCC. In this study we characterized one candidate TSG, TAT, at 16q22.1.…”

Section: Discussionmentioning

confidence: 99%

“…1 It is believed that the pathogenesis of HCC is a long-term process that involves multiple genetic alterations. Deletion of 16q is one of the most frequent chromosomal alterations in primary HCC, as observed in studies using loss of heterozygosity (LOH) 2 and comparative genomic hybridization (CGH). 3 In our previous CGH study the loss of 16q was observed at a strikingly high rate of 70% in 50 primary HCC cases and this deletion may be an early event in the pathogenesis of HCC.…”

mentioning

confidence: 99%

“…3 Loss of tumor suppressor gene (TSG), E-cadherin at 16q22, has been reported in hepatitis B virus-associated HCC. 4 Using a fine mapping strategy, several distinct minimal deleted regions on 16q were found, 2 suggesting the existence of other TSGs on 16q associated with HCC pathogenesis. In order to isolate down-regulated transcripts at 16q, complementary DNAs (cDNAs) generated from a primary HCC tumor with the loss of 16q have been applied to subtract cDNAs generated from its matched nontumor liver tissue.…”

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confidence: 99%

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Down-regulation of tyrosine aminotransferase at a frequently deleted region 16q22 contributes to the pathogenesis of hepatocellular carcinoma

Dong²,

Xie³

et al. 2010

Hepatology

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Loss of 16q is one of the most frequent alterations in many malignancies including hepatocellular carcinomas (HCC), suggesting the existence of a tumor suppressor gene (TSG) within the frequently deleted region. In this report we describe the identification and characterization of one candidate TSG, tyrosine aminotransferase gene (TAT), at 16q22.1. Loss of one TAT allele was detected in 27/50 (54%) of primary HCCs by quantitative real-time polymerase chain reaction. In addition, homo-deletion of TAT alleles was detected in two cases. Down-regulation of TAT was detected in 28/50 (56%) of HCCs, which was significantly associated with the loss of TAT allele and hypermethylation of TAT 5 0 CpG island (CGI) region (P < 0.001). Functional studies found that TAT has a strong tumor suppressive ability. Introduction of the TAT gene into HCC cell lines could effectively inhibit colony formation in soft agar, foci formation, and tumor formation in nude mice. Further study found that the tumor suppressive mechanism of TAT was associated with its proapoptotic role in a mitochondrial-dependent manner by promoting cytochrome-c release and activating caspase-9 and PARP. Conclusion: Taken together, our findings suggest that TAT plays an important suppressive role in the development and progression of HCC.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Down-regulation of tyrosine aminotransferase at a frequently deleted region 16q22 contributes to the pathogenesis of hepatocellular carcinoma

Dong²,

Xie³

et al. 2010

Hepatology

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“…In addition, chromosome 16q24.2-24.3 is one of the frequent regions of allelic losses in human HCC. 24,36 T-cadherin is located in this region and has been documented to be underexpressed in a number of human cancers. [6][7][8][9][10] The high correlation between LOH results and T-cadherin expression status (59.5%) suggests that allelic loss of T-cadherin may also be a crucial mechanism in the silencing of T-cadherin expression in HCC.…”

Section: Discussionmentioning

confidence: 99%

“…24 Therefore, we analyzed the allelic losses with LOH assay using 2 microsatellite markers (D16S3091 and D16S402) flanking the T-cadherin locus. Of the 49 HCC cases, 42 were successfully examined for LOH at the D16S3091 and D16S402 loci, and LOH was found in 32.4% (12 of 37 informative cases) and 37.5% (15 of 40 informative cases) ( Fig.…”

Section: Allelic Loss Of T-cadherin In Human Hccmentioning

confidence: 99%

Genetic and epigenetic inactivation of T‐cadherin in human hepatocellular carcinoma cells

Chan

Lee

Chan

et al. 2008

Intl Journal of Cancer

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T-cadherin is an atypical cadherin and growing evidence has indicated that T-cadherin exerts tumor-suppressive effects on cancers of epithelial cell type and also causes positive effects on tumor angiogenesis. Human hepatocellular carcinoma (HCC) is a hypervascular tumor and T-cadherin has been shown to be overexpressed in intratumoral endothelial cells of HCCs. However, the expression status and functions of T-cadherin in hepatocytes or HCC cells remain unclear. Here, we demonstrated that T-cadherin was underexpressed in HCC cells (26.5%, 13/49 cases), but was frequently (77.6%, 38/49) overexpressed in intratumoral endothelial cells immunohistochemically. Semiquantitative RT-PCR analysis also showed that the T-cadherin gene was underexpressed in 7 of 11 HCC cell lines. Loss of heterozygosity analysis revealed that 32-38% of the 42 human HCC samples had allelic losses at this locus. Upon pharmacological treatment with demethylating agent 5-aza-2 0 -deoxycytidine or histone deacetylase inhibitor trichostatin A, T-cadherin promoter hypermethylation and/or histone deacetylation was frequently observed in HCC samples and cell lines. Functionally, enforced expression of T-cadherin induced G 2 /M cell cycle arrest, reduced cell proliferation in low serum medium, suppressed anchorage-independent growth in soft agar and increased sensitivity to TNFa-mediated apoptosis in HCC cells. Intriguingly, we found that T-cadherin significantly suppressed the activity of c-Jun, a crucial oncoprotein constitutively activated in HCC cells. To conclude, T-cadherin was differentially expressed in human HCCs. The underexpression of T-cadherin in HCC cells suggests it may be another critical event in addition to T-cadherin-mediated angiogenesis during HCC development.

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Identification of a 1-Mb common region at 16q24.1-24.2 deleted in hepatocellular carcinoma

Bando

Nagai

Matsumoto

et al. 2000

Genes Chromosom. Cancer

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Deletion mapping of chromosome 16q in hepatocellular carcinoma

Cited by 30 publications

References 16 publications

Down-regulation of tyrosine aminotransferase at a frequently deleted region 16q22 contributes to the pathogenesis of hepatocellular carcinoma

Down-regulation of tyrosine aminotransferase at a frequently deleted region 16q22 contributes to the pathogenesis of hepatocellular carcinoma

Genetic and epigenetic inactivation of T‐cadherin in human hepatocellular carcinoma cells

Identification of a 1-Mb common region at 16q24.1-24.2 deleted in hepatocellular carcinoma

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