Frequent allelic loss on chromosomes 4q and 16q associated with human hepatocellular carcinoma in Taiwan

Chou, Yah Huei Wu; Chung, Kuo Chen; Jeng, Long Bin; Chen, Tse Ching; Liaw, Yun Fan

doi:10.1016/s0304-3835(97)00276-0

Cited by 31 publications

(22 citation statements)

References 22 publications

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“…A tumour-suppressor gene relevant for HCC development has already been suspected at this location from several LOH studies (frequency: 17-77%) (Buetow et al, 1989;Zhang et al, 1990;Konishi et al, 1993;Yeh et al, 1996;Chou et al, 1998). A common chromosomal breakpoint mapped to 4q has also been found in 4 out of 50 HCCs (Pasquinelli et al, 1988) as well as an HBV integration site in an HCC at 4q32.1.…”

Section: Discussionmentioning

confidence: 94%

Frequent genomic imbalances suggest commonly altered tumour genes in human hepatocarcinogenesis

Niketeghad

Decker²,

Caselmann

et al. 2001

Br J Cancer

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Summary Hepatocellular carcinoma (HCC) is one of the most frequent-occurring malignant tumours worldwide, but molecular changes of tumour DNA, with the exception of viral integrations and p53 mutations, are poorly understood. In order to search for common macroimbalances of genomic tumour DNA, 21 HCCs and 3 HCC-cell lines were characterized by comparative genomic hybridization (CGH), subsequent database analyses and in selected cases by fluorescence in situ hybridization (FISH). Chromosomal subregions of 1q, 8q, 17q and 20q showed frequent gains of genomic material, while losses were most prevalent in subregions of 4q, 6q, 13q and 16q. Deleted regions encompass tumour suppressor genes, like RB-1 and the cadherin gene cluster, some of them previously identified as potential target genes in HCC development. Several potential growth-or transformation-promoting genes located in chromosomal subregions showed frequent gains of genomic material. The present study provides a basis for further genomic and expression analyses in HCCs and in addition suggests chromosome 4q to carry a so far unidentified tumour suppressor gene relevant for HCC development.

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Section: Discussionmentioning

confidence: 94%

Frequent genomic imbalances suggest commonly altered tumour genes in human hepatocarcinogenesis

Niketeghad

Decker²,

Caselmann

et al. 2001

Br J Cancer

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“…This gene maps to chromosome 4q25-q26. This region is commonly deleted in human breast cancer (Tirkkonen et al, 1997;Schwendel et al, 1998), ovarian cancer (Sonoda et al, 1997), lung cancer (Shivapurkar et al, 1999), hepatoma (Chou et al, 1998;Piao et al, 1998), cervical cancer (Mitra et al, 1994), head and neck squamous cell carcinoma (Pershouse et al, 1997), colon cancer (Arribas et al, 1999), and oral cancer (Wang et al, 1999). A candidate for the iris hypoplasia locus also maps on 4q25 (Heon et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

PRDM5 is silenced in human cancers and has growth suppressive activities

Deng

Huang

2004

Oncogene

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Several genes that contain the PR (PRDI-BF1 and RIZ) domain have been linked with human cancers. We describe here a new PR-domain-containing gene designated as PRDM5 (PFM2). A PRDM5 cDNA was isolated based on its homology to the PR domain of RIZ1 (PRDM2). The gene encodes an open reading frame of 630 amino acids and contains a PR domain in the NH-terminal region followed by 16 zinc finger motifs. Radiation hybrid analysis mapped PRDM5 to human chromosome 4q26, a region thought to harbor tumor suppressor genes for breast, ovarian, liver, lung, colon, and other cancers. The gene has a CpG island promoter and is silenced in human breast, ovarian, and liver cancers. A recombinant adenovirus expressing PRDM5 caused G2/M arrest and apoptosis upon infection of tumor cells. These results suggest that inactivation of PRDM5 may play a role in carcinogenesis.

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“…The alteration of 1p as an early event in HCC has been implicated previously. 33 Although genetic alterations in 4q in HCC have been documented, 14,17,33,37,38 their relevance to the development and stage of HCC has not been determined. The role of genetic alteration in the 4q and 4q28 region in particular on the initiation and progression of HCC should be further examined.…”

Section: Discussionmentioning

confidence: 99%

Multiple Genetic Alterations, 4Q28, A New Suppressor Region, and Potential Gender Differences in Human Hepatocellular Carcinoma

Hammond¹,

Jeffers²,

Carr³

et al. 1999

Hepatology

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Primary hepatocellular carcinomas (HCCs) of different etiologies were studied to determine the rate of alteration of several genetic regions previously associated with the HCC phenotype. The focus of our study was to identify the frequency of genetic alterations within individual HCCs and their distribution among male and female cases. Genetic differences were evaluated between DNA isolated from tumor (T) and corresponding non-tumor (N) tissue using short tandem repeat (STR)-microsatellites and restriction fragment length polymorphism (RFLP) analyses. Twenty-eight HCC cases were studied with polymorphic markers from different parts of the genome. Three or more loci were identified with genetic alterations from 28 loci tested in 63% of HCC cases. Human hepatocellular carcinoma (HCC) remains a leading cause of cancer death worldwide. HCC has a very poor prognosis, and there is only limited understanding of the molecular events that lead to uncontrolled proliferation of the liver parenchymal cells. Several etiologic factors have been identified as high risk factors in association with HCC development, including previous infection with hepatitis B virus (HBV), hepatitis C virus (HCV), exposure to aflatoxin, and alcohol-induced cirrhosis. 1-4 However, it remains unclear how these agents affect hepatocyte growth, the transformation process, or both.Current research has focused on identifying the genetic region(s) in which a mutation leads to transformation in the hepatocyte and malignant proliferation in the liver because neoplasia is thought to result from the initiation and accumulation of genetic mutations in a multistep process. Genetic evolution of the tumor phenotype is best defined in colorectal cancer in which several sequential mutations have been identified in association with the stage of the disease. 5,6 Alterations of several chromosomal regions have been identified in HCC. 7-38 Some data suggest that certain HCC causes are associated with specific genetic alterations. 25,26,36 p53 is the only gene in which specific mutations have been associated with HCC, but even these mutations are recognized as later alterations in HCC development. [26][27][28][29] Epidemiological studies document the higher incidence of HCC among men than women but so far no correlation with genetic data was implicated. A recent study in 120 HCCs documented frequent loss of heterozygosity (LOH) in chromosome regions 1p, 1q, 2q, 4q, 6q, 8p, 9q, 16p, 16q, and 17p. 34 Despite a long list of loci with frequent LOH in HCCs the sequence of these mutations in HCC development is not understood.We and others have identified a high incidence of genetic alteration in the short arm of chromosome 1 in HCCs of different causes. [30][31][32][33] We now report that the majority of our HCC cases have multiple genetic alterations. The most frequent target for genetic change in HCCs analyzed is the 1p36 region. The frequent LOH in 1p36.1, 1p36.3, 4q28, 13q14, and 17p13 indicates important HCC suppressors in the vicinity of these regions. The 4q28 locus...

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Frequent allelic loss on chromosomes 4q and 16q associated with human hepatocellular carcinoma in Taiwan

Cited by 31 publications

References 22 publications

Frequent genomic imbalances suggest commonly altered tumour genes in human hepatocarcinogenesis

Frequent genomic imbalances suggest commonly altered tumour genes in human hepatocarcinogenesis

PRDM5 is silenced in human cancers and has growth suppressive activities

Multiple Genetic Alterations, 4Q28, A New Suppressor Region, and Potential Gender Differences in Human Hepatocellular Carcinoma

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