Allele loss on chromosome 16 associated with progression of human hepatocellular carcinoma.

Tsuda, Hitoshi; Zhang, Wandong; Shimosato, Yukío; Yokota, Jun; Terada, Masaaki; Sügimura, Takashi; Miyamura, Tatsuo; Hirohashi, Setsuo

doi:10.1073/pnas.87.17.6791

Cited by 252 publications

(155 citation statements)

References 53 publications

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“…Loss of heterozygosity at 1p appears to occur at an early stage of carcinogenesis, and loss of heterozygosity at 16q is associated with progression of HCC. 22,23 Our present results together with those of other studies suggest that FGR/SRC2 and CYLD are associated with hepatocarcinogenesis.…”

Section: Discussionsupporting

confidence: 86%

Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH

Hashimoto

Mori²,

Tamesa³

et al. 2004

Modern Pathology

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To clarify the genetic aberrations involved in the development and progression of hepatitis C virus-associated hepatocellular carcinoma (HCV-HCC), we investigated DNA copy number aberrations (DCNAs) in 19 surgically resected HCCs by conventional CGH and array CGH. Conventional CGH revealed that increases of DNA copy number were frequent at 1q (79% of the cases), 8q (37%), 6p (32%), and 10p (32%) and that decreases were frequent at 17p (79%), 16q (58%), 4q (53%), 13q (42%), 10q (37%), 1p (32%), and 8p (32%). In general, genes that showed DCNAs by array CGH were usually located in chromosomal regions with DCNAs detected by conventional CGH analysis. Increases in copy numbers of the LAMC2, TGFB2, and AKT3 genes (located on 1q) and decreases in copy numbers of FGR/SRC2 and CYLD (located on 1p and 16q, respectively) were observed in more than 30% of tumors, including small, well-differentiated carcinomas. These findings suggest that these genes are associated with the development of HCV-HCC. Increases of MOS, MYC, EXT1, and PTK2 (located on 8q) were detected exclusively in moderately and poorly differentiated tumors, suggesting that these alterations contribute to tumor progression. In conclusion, chromosomal and array CGH technologies allow identification of genes involved in the development and progression of HCV-HCC.

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Section: Discussionsupporting

confidence: 86%

Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH

Hashimoto

Mori²,

Tamesa³

et al. 2004

Modern Pathology

View full text Add to dashboard Cite

show abstract

“…Chromosome 16q demonstrated LOH in 54% of the tested ERMS between the markers D16S752 and D16S539 on chromosome band 16q23-16qter. Chromosome 16q is also frequently a ected in Wilms' tumors, 20% (Maw et al, 1992), hepatocellular carcinoma, 30% (Tsuda et al, 1990), prostate, 30% (Carter et al, 1990) and breast cancers, 52% (Tsuda et al, 1994). Recently, Weber-Hall et al (1996) demonstrated 16q LOH in 40% of the tested ERMS by comparative genomic hybridization which con®rms our allelotype data.…”

Section: Discussionsupporting

confidence: 85%

Allelotype of pediatric rhabdomyosarcoma

et al. 1997

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An allelotype covering all autosomes was constructed for the embryonal form of childhood rhabdomyosarcoma (ERMS) in order to identify regions encompassing tumorsuppressor genes (TSG) involved in ERMS. Thusfar most studies were focussed on chromosome 11p15.5, which frequently shows loss of heterozygozity (LOH) in embryonal tumors like RMS and Wilms' tumor (WT). In this study we show that, besides LOH of chromosome 11p15.5 (72%), LOH of chromosome 16q was present in 54% of the tumors analysed. Delineation of these two regions shows that the smallest region of overlap (SRO) for chromosome 11 was between D11S988 and D11S922. This region, estimated to be 7 cM and 3-5 Mb, is also the location of the putative Wilms' tumor WT2 TSG. It contains several genes including IGF2 and potential tumorsuppressor genes like H19 and p57 kip2 , which might contribute to the carcinogenesis of RMS. Analysis of chromosome 16q LOH de®ned the SRO between D16S752 and D16S413. LOH of chromosome 16 is also found in other tumors, including WT. Our data suggest that genes involved in the development of RMS and WT may not only be similar for chromosome 11 but also for chromosome 16.

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“…LOH of chromosome 16q was observed in a variety of human cancers and reported to be associated with the progression of HCC, suggesting the loss of some genes in this region may be involved in the enhancement of tumor aggressiveness [29]. The common deletion region on 16q could be defined to 16q21-q23 (between D16S503 and D16S3091), as shown in this study.…”

Section: Discussionsupporting

confidence: 67%

Genetic aberration in primary hepatocellular carcinoma: correlation between p53 gene mutation and loss-of-hetero- zygosity on chromosome 16q21-q23 and 9p21-p23

et al. 2000

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To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC), we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on chromosome 9, 16 and 17. Loss-of-heterozygosity (LOH) is observed with high frequency on chromosomal region 17p13 (36/55, 65 %), 9p21-p23 (28/55, 51%), 16q21-q23 (27/55, 49 %) in tumors. Meanwhile, microsatellite instability is rarely found in these microsatellite loci. Direct sequencing was performed to detect the tentative mutation of tumor suppressor genes in these regions: p53, MTS1/p16, and CDH1/E-cadherin. Within exon 5-9 of p53 gene, 14 out of 55 HCC specimens (24 %) have somatic mutations, and nucleotide deletion of this gene is reported in HCC for the first time. Mutation in MTS1/p16 is found only in one tumor case. We do not find mutations in CDH1/E-cadherin. Furthermore, a statistically significant correlation is present between p53 gene mutation and loss of chromosome region 16q21-q23 and 9p21-p23, which indicates that synergism between p53 inactivation and deletion of 16q21-q23 and 9p21-p23 may play a role in the pathogenesis of HCC.

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Allele loss on chromosome 16 associated with progression of human hepatocellular carcinoma.

Cited by 252 publications

References 53 publications

Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH

Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH

Allelotype of pediatric rhabdomyosarcoma

Genetic aberration in primary hepatocellular carcinoma: correlation between p53 gene mutation and loss-of-hetero- zygosity on chromosome 16q21-q23 and 9p21-p23

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