Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By restriction fragment length polymorphism (RFLP) analysis, it was found that loss of heterozygosity (LOH) at three different chromosomal loci, 3p, 13q, and 17p, occurs simultaneously in nearly 100% of small-cell lung carcinomas (SCLC). This was observed even in stage I tumors and an untreated tumor, and it occurred prior to NMYC amplification. The common region of LOH on chromosome 3p was 3p14-24.1, and this region was also frequently lost in carcinoma of the uterine cervix (100% at D3S2 on 3p14-21) as well as renal cell carcinoma (56% at ERBA beta on 3p22-24.1), suggesting the presence of tumor suppressor gene(s) for these cancers in this region. On chromosome 13, LOH was observed commonly in the region between 13q12 and 13q22, including the RB locus on 13q14, and normal RB protein was not detected in any of 9 SCLC cell lines by immunoprecipitation analysis. The common region of LOH on chromosome 17 was 17p13 and is the same as that in colon carcinoma and osteogenic sarcoma. Since LOH is supposed to unmask the recessive mutation of tumor suppressor gene in the remaining allele, these results may imply that at least six genetic alterations are necessary to convert a normal cell into a fully malignant cancer cell in SCLC. RFLP analysis was performed on several other types of human cancers, including carcinoma of the uterine cervix, neuroblastoma, hepatocellular carcinoma, pheochromocytoma, and stomach cancer to determine the chromosomal loci of putative tumor suppressor genes in each tumor. Chromosomal loci showing frequent LOH were different among these tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Multiple genetic alterations in small-cell lung carcinoma. 257 37

To investigate cumulative genetic changes during development and progression of hepatocellular carcinoma (HCC), we examined DNAs isolated from 104 tumors for loss of heterozygosity (LOH) at 13 loci on six chromosomal arms and for an increase of copy number ("multiplication") of alleles on 8q, using polymorphic microsatellite markers. A comparison of genetic features with clinicopathological stages of these tumors revealed that LOH on 1p had occurred in tumors at an early stage or with a well-differentiated histological phenotype (8/26; 31%) as well as in tumors at more advanced stages. Genetic alterations on chromosome arms 4q, 8p, 8q, 13q, 16q, and 17p were more often observed in tumors of more advanced stages and poorer differentiation grades. When size was the criterion for comparison, LOH on 1p was observed frequently even in tumors smaller than 2 cm (6/16; 38%), whereas allelic losses on 16q were detected frequently only in larger tumors. These results suggest that the putative tumor suppressor gene(s) assumed to be located on 1p may be involved in an early step of carcinogenesis in liver tissue and that the other genetic alterations examined here may play important roles in progression of HCC.
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PMID:Accumulation of genetic changes during development and progression of hepatocellular carcinoma: loss of heterozygosity of chromosome arm 1p occurs at an early stage of hepatocarcinogenesis. 766 35

Cytogenetic analysis of hepatocellular carcinoma (HCC) cell lines and primary HCC tissues has demonstrated chromosome 1p to be the region most commonly affected. To refine the altered locus, genetic abnormalities of this region were surveyed systemically by microsatellite polymorphism analysis. Twelve sets of primers evenly distributed on chromosome 1p which can amplify di- or tetranucleotide repeat length polymorphism by polymerase chain reaction were selected. The results were then supplemented by the conventional restriction fragment length polymorphism study. A comparison of the allele patterns between 30 pairs of HCC and their corresponding nontumor DNAs discovered chromosome 1p aberrations in 15 of 30 tumors (50%). The abnormalities can be classified into three groups. The first aberration was typical loss of heterozygosity that was found in 9 HCCs (30%). The second aberration was a 2-3-fold increase of allelic dosage, which was detected in 6 HCCs (20%). The third aberration was the novel microsatellite polymorphism, which was detected in 3 cases (10%). These abnormalities seemed to cluster at the distal part of chromosome 1p, with a common region mapped to 1p35-36, which is also the region with frequent loss of heterozygosity in neuroblastoma and colorectal and breast cancers. Therefore, loss of putative tumor suppressor gene(s) in this locus may participate in the development of hepatocellular carcinoma and a wide range of human cancers.
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PMID:Frequent genetic alterations at the distal region of chromosome 1p in human hepatocellular carcinomas. 791 13

We have previously shown that the tumor suppressor gene for hepatocellular carcinoma (HCC) without cirrhosis may be located on chromosome 5q35-qter. In this study, we analyzed nine cases of primary HCC without cirrhosis using probes from the MCC and APC genes, which are in the region 5q21-22. None of the informative cases had allele loss detected by these probes, whereas the probe lambda MS8 for the region 5q35-qter showed allele loss in six out of six informative cases. The results confirm that the putative tumor suppressor gene for HCC without cirrhosis on chromosome 5q is distinct from the MCC and APC genes.
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PMID:The putative tumor suppressor gene on chromosome 5q for hepatocellular carcinoma is distinct from the MCC and APC genes. 840 27

Although the occurrence of loss of genetic material in hepatocellular carcinoma (HCC) has been documented both by cytogenetic analysis and by monitoring of allelic losses, a global overview of the extent and frequency of deletion occurring throughout the genome is not yet available. To contribute to this information, DNAs extracted from flow-sorted aneuploid nuclei from HCC and matched normal DNAs were typed for 275 microsatellite loci that were distributed along the autosomes. An average of 190 (69%) informative loci per case were generated on 48 HCC. Complete loss of heterozygozity in the tumor DNA was observed for 15.6% of the typed loci. The chromosome segments that were most frequently affected by deletion were: 8p (60%), 17p (48%), 1p (44%), 4q (42%), 16p (40%), 16q (39%), 6q (35%), 9p (30%), and 13q (29%). On average, 8 of the 39 chromosome segments studied per tumor carried at least one locus that demonstrated loss of heterozygosity (ie., the fractional allelic loss was 0.21). Groups of concerted nonsyntenic losses were observed for 16p and 1p and for 16p and 4q. The location of putative tumor suppressor genes on the most frequently deleted regions was confirmed and, in some cases, refined.
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PMID:Concerted nonsyntenic allelic losses in hyperploid hepatocellular carcinoma as determined by a high-resolution allelotype. 915 95

Codon 249 (exon 7) of the putative tumor suppressor gene p53 is a mutational hot-spot for hepatocellular carcinoma (HCC) but not other tumors. DNA samples from primary HCC patients from Tongan, an area of high HCC incidence in China (> 40 per 100,000 population), were analyzed for specific mutations in codon 249 of the p53 gene using polymerase chain reaction (PCR)/restriction-digest methods and direct DNA sequencing. Seven of the 21 samples screened were found to have a point mutation at the third base position of codon 249 (AGG to AGT). The result is consistent with previous reports that the G-->T transversion is positively associated with the level of dietary aflatoxin B1 (AFB1) contamination, which has been implicated as one of the risk factors in Tongan area. Of the 7 HCC patients that contained the codon 249 point mutation, one was hepatitis B virus (HBV)-negative. This is only the second documentation of an HCC patient harboring the p53 codon 249 mutation, who was HBV-negative.
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PMID:Mutations at codon 249 of p53 gene in human hepatocellular carcinomas from Tongan, China. 940 27

To define the critical region of liver-specific tumor suppressor genes in human hepatocellular carcinoma (HCC), we analyzed 30 cases of hepatocellular carcinoma using nine 4q and six 16q microsatellite polymorphic DNA markers. We observed one major common deleted region which was flanked by D4S175-D4S1625 and there may be two tumor suppressor genes on chromosome 16q associated with HCC. An extensive study of allelotyping of human HCC was therefore carried out in the candidate region on arms of chromosome 4q with additional tumor tissues and more informative microsatellite DNA markers. These data imply that at least one putative tumor suppressor gene is located in the human chromosome 4q26-q27 region and provides very useful information for further construction of a long-range physical restriction map and thereafter cloning of the putative tumor suppressor gene.
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PMID:Frequent allelic loss on chromosomes 4q and 16q associated with human hepatocellular carcinoma in Taiwan. 946 Oct 10

Hepatocellular carcinoma (HCC) frequently shows a loss of heterozygosity (LOH) on chromosome 4q. In order to define the commonly affected region on chromosome 4q for further positional cloning of the putative tumor suppressor gene, we carried out allelic imbalance (AI) studies in 41 HCCs using a panel of 43 microsatellite markers. Thirty-four cases (82.9%) showed AI at one or more loci. Detailed deletion mapping identified 7 independent, frequently deleted regions on this chromosome arm. These were the (1) D4S1615 locus, (2) D4S1598 locus, (3) D4S620 locus, (4) D4S1566 and D4S2979 loci, (5) D4S1617 and D4S1545 loci, (6)D4S1537 locus; and (7) from the D4S2920 to D4S2954 locus. Among these 7 frequently deleted regions, 5 were associated with tumor differentiation. Our results suggest that several putative tumor suppressor genes may be present on chromosome 4q and that the AI of chromosome 4q may play a role in the aggressive progression of HCC.
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PMID:Deletion mapping of chromosome 4q in hepatocellular carcinoma. 969 26

To identify the location of one or more of the putative tumor suppressor genes (TSG) on chromosome arm 4q that may be involved in hepatocellular carcinoma (HCC), we examined 96 primary HCCs for their patterns of allelic loss at 39 microsatellite marker loci distributed along this chromosome arm. Allelic loss at one or more loci was observed in 71 (74%) HCCs. Detailed deletion mapping identified two distinct commonly deleted regions; one was located within a 1-cM interval flanked by D4S1534 and D4S2929 at 4q21-22, the other in the 1-cM interval flanked by D4S2921 and D4S2930 at 4q35. Of the tumors for which clinical data were available, allelic loss at 4q35 was more frequent in poorly or moderately differentiated tumors than in well-differentiated tumors (3/15, 20%, vs. 14/21, 67%, P = 0.008); in tumors larger than 2 cm in size (2/11, 18%, vs. 34/62, 55%, P = 0.046); and in tumors that arose from liver cirrhosis as opposed to HCCs arising from chronic hepatitis (25/42, 60%, vs. 9/27, 33%, P = 0.048). The association of allelic losses on 4q35 with larger tumor size and aggressive histological type implies that loss or inactivation of TSG located within the 1-cM interval of 4q35 identified here contribute to progression of HCCs.
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PMID:Identification of a 1-cM region of common deletion on 4q35 associated with progression of hepatocellular carcinoma. 1037 75

To identify the location of the putative tumor suppressor gene on chromosome 16p that may be involved in hepatocellular carcinoma (HCC), we examined 96 primary HCCs and evaluated their patterns of allelic loss at 10 microsatellite marker loci distributed along this chromosome arm. Allelic loss at one or more loci was observed in 46 (48%) of these tumors. Through detailed deletion mapping of tumors having partial or interstitial deletions, we identified a commonly deleted region at a 1-cM interval, flanked by D16S519 and D16S3078 at 16p13.13, defining the location of a putative tumor suppressor gene for HCC. This region contains the gene for JAB (JAK-binding protein), which is responsible for negative-feedback regulation of the JAK-STAT pathway induced by cytokine stimulation, raising the possibility that inactivation of this gene may participate in hepatocarcinogenesis via genetic and/or epigenetic changes.
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PMID:Localization of a target region of allelic loss to a 1-cM interval on chromosome 16p.13.13 in hepatocellular carcinoma. 1055 23


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