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

Y. Soini, S. C. Chia, W. P. Bennett, John Davis 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, C. C. Harris

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Abstract

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 B1 (AFB1) is an AGG(arg)→AGT(ser) missense mutation in codon 249 of the p53 gene. We analyzed HCCs from Monterrey, Mexico, for the codon 249(ser) 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 antiserum (CM-1). Eight of 21 cases were positive by p53 immunohistochemistry. Of the 16 cases sequenced for exon 7 of p53 three codon 249 AGG(arg)→AGT(ser) 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.

Original languageEnglish (US)
Pages (from-to)1007-1012
Number of pages6
JournalCarcinogenesis
Volume17
Issue number5
DOIs
Publication statusPublished - May 1996

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ASJC Scopus subject areas

  • Cancer Research

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