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

作者：Soini Y; Chia SC; Bennett WP; Groopman JD; Wang JS; DeBenedetti VMG; Cawley H; Welsh JA; Hansen C; Bergasa NV; Jones EA; DiBisceglie AM; Trivers GE; Sandoval CA; Calderon IE; Espinosa LEM; Harris CC

来源：Carcinogenesis, 1996, 17(5): 1007-1012.

DOI：10.1093/carcin/17.5.1007

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.

• 出版日期1996-5