Chromosomal allelic imbalance evolving from liver cirrhosis to hepatocellular carcinoma

Yeh, Shiou–Hwei; Chen, Pei‐Jer; Shau, Wen–Yi; Chen, Yawen; Lee, Po–Huang; Chen, Jung‐Ta; Chen, Ding‐Shinn

doi:10.1053/gast.2001.27211

Cited by 88 publications

(75 citation statements)

References 40 publications

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“…The marker pairs selected for HCC (74 markers from 17 chromosomal arms) included 1p (D1S160, D1S163, D1S170, D1S186, MYCL), 3p (D3S1317), 4p (D4S394), 4q (D4S398, D4S395, D4S392, D4S422, FGA, FABP2, D4S427, D4S415, D4S1615, D4S1554, D4S1426, D4S1598, D4S620, D4S1566, D4S1545, D4S2920, D4S2943, D4S2954), 5q (D5S409), 6q (D6S264), 8p (D8S261, D8S277), 8q (D8S85, D8S200, D8S555, D8S283), 9p (D9S169, D9S1747, D9S104), 10q (D10S109), 11p (D11S554, D11S436, D11S1344, D11S932, D11S1324), 11q (D11S938, D11S29), 12p (D12S93), 13q (D13S171, D13S153, Rb1, D13S133, D13S227, D13S159, D13S166, D13S168), 14q (D14S72, D14S51), 16p (D16S419, D16S409, D16S3106, D16S498), 16q (D16S415, D16S408, D16S512, D16S289, D16S402, D16S516, D16S422, D16S413), and 17p (D17S520, D17S1176, TP53, D17S513, D17S578, D17S796, D17S849) based on previous reports (Yeh et al, 1996;Nagai et al, 1997;Piao et al, 1998;Fujii et al, 2000;Okabe et al, 2000;Yeh et al, 2001). The marker pairs selected for CC (35 markers from 16 chromosomal arms) included 2p (BAT-26), 3p (D3S3667, D3S1578, D3S3582, D3S3560, D3S1581, D3S3729, D3S1588, D3S3648), 4 (D4S415, D4S413), 5q (D5S323, D5S417), 6p (D6S263), 6q (D6S292), 7q (D7S495, D7S486), 9p (D9S747, D9S171), 11p (D11S907, D11S569), 14q (D14S1436), 16q (D16S3094, D16S511, D16S534, D16S520), 17 (D17S695), 18q (D18S67, D18S51, D18S535), 20 (D20S85), 21q (D21S1245, D21S1436, D21S1270), and Xp (DXS538) (Ding et al, 1993;Fujii et al, 2000).…”

Section: Analysis For Allelic Lossmentioning

confidence: 99%

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Molecular diagnosis of primary liver cancer by microsatellite DNA analysis in the serum

Chang¹,

Ho²,

Chen³

et al. 2002

Br J Cancer

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Frequent loss of heterozygosity of microsatellites markers on specific chromosomal region have been reported in various types of primary human cancer. The same loss of heterozygosity has also been identified in the matched plasma/serum DNA. Using 109 microsatellite markers representing 24 chromosomal arms, we have examined the loss of heterozygosity in 21 cases of hepatocellular carcinoma, six of cholangiocarcinoma, and 27 cases of chronic hepatitis or cirrhosis. All cases of the hepatocellular carcinoma showed deletion from two to 10 chromosomal arms, while deletion of chromosomes from two to eight regions was detected in five of six cholangiocarcinoma patients. One or more loss of heterozygosity in the paired serum DNA could be detected in 16 of 25 (76.2%) hepatocellular carcinoma patients. In contrast, no alterations in serum DNA test could be found in cholangiocarcinoma patients. Five of seven (71.4%) hepatocellular carcinoma patients with alpha-fetoprotein levels less than 20 ng ml 71 produced positive serum DNA test. The profiles of 19 microsatellite markers gave a 100% positive predictive value and an 80.8% negative predictive value for hepatocellular carcinoma. In conclusion, we have determined a profile of microsatellite markers appropriate for differential diagnosis of primary liver cancer. The discovery may permit a high-throughput screening of hepatocellular carcinoma at an early stage of disease.

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Section: Analysis For Allelic Lossmentioning

confidence: 99%

“…However, a recent study reported that around 50% of the cirrhotic nodules are monoclonal and already have chromosomal aberrations (Yeh et al, 2001). Whether the aberrations are also present in the serum DNA is currently unknown.…”

Section: Genetics and Genomicsmentioning

confidence: 99%

Molecular diagnosis of primary liver cancer by microsatellite DNA analysis in the serum

Chang¹,

Ho²,

Chen³

et al. 2002

Br J Cancer

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“…As in other solid tumors, a large number of genetic alterations are accumulated during the carcinogenetic process. Indeed, genetic and epigenetic alterations have been observed in cirrhotic nodules and half of them have been found to have a monoclonal origin by examining the X-chromosome methylation pattern (Piao et al, 1997;Paradis et al, 1998;Yeh et al, 2001). Chromosome aberrations with loss of alleles are found in half of cirrhotic nodules and more frequently in nodules with small cell dysplasia (Yeh et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, genetic and epigenetic alterations have been observed in cirrhotic nodules and half of them have been found to have a monoclonal origin by examining the X-chromosome methylation pattern (Piao et al, 1997;Paradis et al, 1998;Yeh et al, 2001). Chromosome aberrations with loss of alleles are found in half of cirrhotic nodules and more frequently in nodules with small cell dysplasia (Yeh et al, 2001). However, structural alterations of specific gene, that is, activating mutations of oncogene and inactivating mutations of tumor suppressor genes have not been described in cirrhosis and were only found in HCC and liver cell adenomas.…”

Section: Introductionmentioning

confidence: 99%

Genetics of hepatocellular tumors

2006

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Numerous genetic alterations are accumulated during the process of hepatocarcinogenesis. These genetic alterations can be divided into two groups. The first set of genetic alterations is specific of hepatocellular tumor risk factors. It includes integration of hepatitis B virus (HBV) DNA, R249S TP53 (tumor protein p53) mutation in aflatoxin B1-exposed patients, KRAS mutations related to vinyl chloride exposure, hepatocyte nuclear factor 1a (HNF1a) mutations associated to hepatocellular adenomas and adenomatosis polyposis coli (APC) germline mutations predisposing to hepatoblastomas. The second set of genetic alterations are etiological nonspecific, it includes recurrent gains and losses of chromosomes, alteration of TP53 gene, activation of WNT/b-catenin pathway through CTNNB1/b-catenin and AXIN (axis inhibition protein) mutations, inactivation of retinoblastoma and IGF2R (insulin-like growth factor 2 receptor) pathways through inactivation of RB1 (retinoblastoma 1), P16 and IGF2R. Comprehensive analyses of these genetic alterations have defined two pathways of hepatocarcinogenesis according to the presence or the absence of chromosomal instability. Hepatitis B virus and poorly differentiated tumors are related to chromosome instable tumors associated with frequent TP53 mutations, whereas non-HBV and well-differentiated tumors are related to chromosomal stable samples that are frequently b-catenin activated. These classifications have clinical relevance as genetic alterations may also be related to prognosis.

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“…LOH at microsatellite markers on chromosome 4q was observed in more than 40% of sporadic HCCs, and high rates of LOH on this region were associated with HBV infection (Yeh et al, 1996;Piao et al, 1998;reviewed in Buendia, 2000;Okabe et al, 2000;Laurent-Puig et al, 2001;Bluteau et al, 2002; reviewed in Thorgeirsson and Grisham, 2002). Allelic loss at 4q is of great interest because it is also prevalent in cirrhotic nodules, which have long been considered to be a premalignant lesion of HCC (Yeh et al, 2001), and chromosome 4q contains genes encoding growth factors (e.g. epidermal growth factor) or genes expressed predominantly in the liver (e.g.…”

Section: Introductionmentioning

confidence: 99%

Localization of a susceptibility locus for hepatocellular carcinoma to chromosome 4q in a hepatitis B hyperendemic area

Shih

et al. 2006

Oncogene

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Chromosome 4q is one of the most common regions with a high frequency of allelic loss in hepatocellular carcinoma (HCC). To identify the HCC-susceptibility locus on chromosome 4q, we have performed linkage and familybased association analyses on Chinese families with HCC from Taiwan, where hepatitis B is hyperendemic. Using 77 microsatellite markers spanning chromosome 4q on 52 multiplex families, we found suggestive evidence of linkage to 4q22.3-28.1 with a maximum two-point heterogeneity LOD (HLOD) score of 2.55 at marker D4S3240 on chromosome 4q25. Multipoint analyses with microsatellite markers in the region 4q22.3-28.1 resulted in a maximum HLOD score of 3.12 and a maximum nonparametric linkage (NPL) Z score of 1.98 (pointwise P ¼ 0.0080; region-wide empirical P ¼ 0.021) for D4S3240. The evidence for linkage to D4S3240 was seen mostly in a subset of 28 families lacking affected parents, which showed multipoint HLOD and NPL scores of 3.25 and 2.79 (pointwise P ¼ 0.0028; region-wide empirical P ¼ 0.008), respectively. Family-based association analyses of the 77 microsatellite markers in 191 families (53 multiplex plus 138 singleton families) using the pedigree disequilibrium test provide further support for observed linkage. Additional genotyping in the 52 multiplex families informative for linkage analyses was performed for 29 single-nucleotide polymorphisms around D4S3240. A common haplotype (at markers rs7442180 and rs221330) positioned B873 kb away from D4S3240 was associated with HCC, with P ¼ 0.0074.

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Chromosomal allelic imbalance evolving from liver cirrhosis to hepatocellular carcinoma

Cited by 88 publications

References 40 publications

Molecular diagnosis of primary liver cancer by microsatellite DNA analysis in the serum

Molecular diagnosis of primary liver cancer by microsatellite DNA analysis in the serum

Genetics of hepatocellular tumors

Localization of a susceptibility locus for hepatocellular carcinoma to chromosome 4q in a hepatitis B hyperendemic area

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