- Mutations of the tumor suppressor gene p53 have been found in hepatocellular carcinomas (HCCs) from many countries where HCC is common, but p53 mutations detected by direct sequencing in HCCs from the United States (where HCC is uncommon) have been reported only rarely, p53 Exons 1 to 11 were analyzed by polymerase chain reaction, single-strand conformation polymorphism analysis, and direct sequencing in HCCs from 12 patients from the United States and in adjacent non-tumorous liver from 10 of them. Abnormalities of the p53 gene were found in five of the 12 tumors, including mutations in exon 4 (one patient), exon 5 (one patient) and exon 8 (three patients). In all 12 tumors, a normal conformation of exon 7 was found; in five of these HCCs the absence of mutations was confirmed by direct sequencing. Thus, the mutations of p53 codon 249 that have frequently been found in HCCs from endemic areas apparently do not play a role in most HCCs in the United States. Since the mutations in codon 249 are thought to be due to aflatoxin ingestion, the data suggest that factors other than aflatoxin may be responsible for the p53 abnormalities in the patients from the USA.