Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1864663 (HCC)
 2,985 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HHC is the most common inherited metabolic disease among the white population worldwide, with a gene frequency of about 10% and a frequency of homozygosity of about 1 of 250. Many patients harbor a common haplotype of informative markers on chromosome 6p2l.23, suggesting a strong founder effect exerted by a common Celtic ancestor. With the advent of screening tests (serum Tf saturation, fe), many subjects with HHC are being identified before development of cirrhosis or diabetes mellitus, and early detection is important because prompt and vigorous iron reduction prevents development of such complications and assures normal life expectancy. The HIC can be estimated as accurately by specialized magnetic resonance imaging or susceptometric measurements as by chemical measurements on liver biopsy specimens. However, biopsy specimens retain value for showing fibrosis/cirrhosis and dysplastic hepatocytes, both of which increase risks of HCC development. There is growing evidence that iron in the liver plays an important role in non-HHC diseases, such as alcoholic liver disease, chronic viral hepatitis, and porphyria cutanea tarda. The complicated, manifold roles of iron in pathogenesis of the latter disorder include enhancement of production and irreversible oxidation of uroporphyrinogen, as well as formation of an inhibitor targeted specifically at hepatic uroporphyrinogen decarboxylase. The nature of the gene and gene product that are abnormal in HHC remain elusive, despite the intense efforts of several investigative groups. The search has been hampered by a dearth of informative markers in HHC patients in the relevant region of chromosome 6p. Note added in proof: The cloning of a candidate gene, the mutation of which may perhaps cause HLA-linked hemochromatosis, has just been reported (Feder et al: A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nature (Genetics) 1996;399-408). These workers identified a 250-kb region move than three megabases telomeric of the MHC that was identical in 85% of chromosomes of HHC patients. Within this region, they identified a gene related to the MHC class I family, termed HLA-H, containing two missense alterations one of which is predicted to inactivate this class of proteins. 83% of 178 patients were homozygous for this mutation (Cys 282Tyr). This variant was also found on 3.2% of control chromosomes, as would be expected for such a common disorder. Functional studies are awaited with great interest.
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PMID:An update on iron metabolism: summary of the Fifth International Conference on Disorders of Iron Metabolism. 878 49

Increased expression of epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase, is associated with tumor progression in many carcinomas. Epidermal growth factor receptor inhibitors have shown promise in treating some of these tumors. Fibrolamellar hepatocellular carcinoma (FL-HCC) is an aggressive neoplasm that occurs in young patients with no history of cirrhosis. This study examines the expression and gene copy number of EGFR in FL-HCC. Formalin-fixed, paraffin-embedded FL-HCC (n = 13) sections were stained with a monoclonal antibody against EGFR. Fluorescence in situ hybridization analysis was performed using probes against EGFR gene and centromeric region of chromosome 7 (CEP 7). Epidermal growth factor receptor and CEP 7 signals were counted in 50 tumor nuclei per case as well as 300 normal hepatocyte nuclei. The EGFR to CEP 7 signal ratio was calculated for each case. Most (92%, 12/13) of FL-HCC showed strong and diffuse staining with anti-EGFR antibody. Fluorescence in situ hybridization was informative in 11 cases, 10 of which showed extra EGFR gene copy numbers (mean, 3.69; range, 3.13-5.0). Epidermal growth factor receptor was overexpressed in all these cases. The mean number of EGFR signals per cell in FL-HCC was double that of normal hepatocytes (3.69 versus 1.80); the mean EGFR/CEP 7 ratio in tumor cells was 1.05. In conclusion, EGFR is strongly overexpressed on the cell membrane in nearly all cases of FL-HCC. Similar gains of chromosome 7 are observed, indicating that the extra EGFR gene copies are due to polysomy rather than gene amplification. The strong expression of EGFR in FL-HCC tumors suggests that they may respond to treatment with EGFR antagonists.
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PMID:Epidermal growth factor receptor expression and gene copy number in fibrolamellar hepatocellular carcinoma. 1656 14