Journal Article

An aflatoxin-associated mutational hotspot at codon 249 in the <i>p53</i> tumor suppressor gene occurs in hepatocellular carcinomas from Mexico

Y. Soini, S.C. Chia, W.P. Bennett, J.D. Groopman, J.-S. Wang, V.M.G. DeBenedetti, H. Cawley, J-A. Welsh, C. Hansen, N.V. Bergasa, E. A Jones, A.M. DiBisceglie, G.E. Trivers, C.A. Sandoval, I.E. Calderon, L.E.Munoz Espinosa and C.C. Harris

in Carcinogenesis

Volume 17, issue 5, pages 1007-1012
Published in print May 1996 | ISSN: 0143-3334
e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.5.1007
An aflatoxin-associated mutational hotspot at codon 249 in the p53 tumor suppressor gene occurs in hepatocellular carcinomas from Mexico

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The p53 tumor suppressor gene is commonly mutated in human hepatocellular carcinoma (HCC). The most frequent mutation in HCC in populations exposed to a high dietary intake of aflatoxin Bl (AFB1) is an AGGarg→AGTser mis-sense mutation in codon 249 of the p53 gene. We analyzed HCCs from Monterrey, Mexico, for the codon 249ser hotspot mutation. We also analyzed the serum AFB1-albumin adduct levels of the donors and family members to measure the current AFB1 exposure in this population. Moreover, the presence of hepatitis B and/or C viral infection (HBV or HCV) was analyzed serologically in the patients. Tumor cells were microdissected from tissue sections and exon 7 p53 sequences were amplified by polymerase chain reaction from genomic DNA and sequenced directly. The serological tests for anti-p53 antibodies, HBV or HCV were done by ELISA. Immunohistochemical analysis of p53 protein was done using a polyclonal rabbit antisenim (CM-1). Eight of 21 cases were positive by p53 immunohistochemistry. Of the 16 cases sequenced for exon 7 of p53 three codon 249 AGGarg→AGTser mutations were found. Serum antibodies recognizing p53 protein were found in one of 18 patients. Positive serology for HBV and/or HCV was found in 12 of 20 cases. The serum AFB1-albumin adduct levels in this population ranged from 0.54 to 4.64 pmol aflatoxin/mg albumin. These results indicate that dietary AFB1 and hepatitis viruses are etiological agents in the molecular pathogenesis of HCC in this geographic region of Mexico.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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