Mutations in the p53 tumor suppressor gene are common in various human cancers. These mutations vary among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hematopoietic tissues. The type and location of mutations can provide insights into the causes of these cancers and the function of specific p53 regions. Transitions are common in colon, brain, and lymphoid malignancies, while G:C to T:A transversions are frequent in lung and liver cancers. Mutations at A:T base pairs are more common in esophageal carcinomas. Most transitions in colorectal carcinomas, brain tumors, leukemias, and lymphomas occur at CpG dinucleotide hotspots. G to T transversions in lung, breast, and esophageal carcinomas are spread across many codons. In liver tumors from regions with both aflatoxin B1 and hepatitis B virus as risk factors, most mutations occur at codon 249. These differences may reflect the combined influence of exogenous and endogenous factors in human carcinogenesis. The p53 gene is the most common gene mutated in human cancers. The normal p53 gene encodes a 53-kD nuclear phosphoprotein involved in cell proliferation control. Mutant alleles with single base substitutions code for proteins with altered growth regulatory properties. Other genetic changes, such as allelic loss, rearrangements, and deletions, have also been detected in human tumors. These genetic changes, along with alterations in oncogenes and other tumor suppressor genes, contribute to the mutational network leading to malignancy. Analysis of base substitution mutations is important because it can reveal the origins of mutations that lead to human cancers. The positions of mutations in the p53 gene sequence define regions essential for its biological functions and interactions with other proteins. Mutations are found at highly conserved residues of the p53 protein. Most mutations are located in the 600-base pair region of the p53 gene product, which includes exons 5 through 8. These exons contain most of the evolutionarily conserved amino acids. Mutations outside these exons are rare. The location and type of mutations in a specific sequence define a mutational spectrum. When all tumor p53 mutations are grouped together, they identify several codons with high mutation frequencies (hot spots). When examined separately by cancer type, clear differences in spectra emerge, both in the position of hot spots and in the frequency of transitions and transversions. For example, colon and breast cancers have different mutation patterns. G:C to A:T transitions are the majority in colon tumors, while G to T transversions are rare in colorectal cancer but common in breast tumors. Lymphomas and leukemias have similar mutation patterns to colorectal tumors, with CpG dinucleotide transitions being a major fraction of point mutations.Mutations in the p53 tumor suppressor gene are common in various human cancers. These mutations vary among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hematopoietic tissues. The type and location of mutations can provide insights into the causes of these cancers and the function of specific p53 regions. Transitions are common in colon, brain, and lymphoid malignancies, while G:C to T:A transversions are frequent in lung and liver cancers. Mutations at A:T base pairs are more common in esophageal carcinomas. Most transitions in colorectal carcinomas, brain tumors, leukemias, and lymphomas occur at CpG dinucleotide hotspots. G to T transversions in lung, breast, and esophageal carcinomas are spread across many codons. In liver tumors from regions with both aflatoxin B1 and hepatitis B virus as risk factors, most mutations occur at codon 249. These differences may reflect the combined influence of exogenous and endogenous factors in human carcinogenesis. The p53 gene is the most common gene mutated in human cancers. The normal p53 gene encodes a 53-kD nuclear phosphoprotein involved in cell proliferation control. Mutant alleles with single base substitutions code for proteins with altered growth regulatory properties. Other genetic changes, such as allelic loss, rearrangements, and deletions, have also been detected in human tumors. These genetic changes, along with alterations in oncogenes and other tumor suppressor genes, contribute to the mutational network leading to malignancy. Analysis of base substitution mutations is important because it can reveal the origins of mutations that lead to human cancers. The positions of mutations in the p53 gene sequence define regions essential for its biological functions and interactions with other proteins. Mutations are found at highly conserved residues of the p53 protein. Most mutations are located in the 600-base pair region of the p53 gene product, which includes exons 5 through 8. These exons contain most of the evolutionarily conserved amino acids. Mutations outside these exons are rare. The location and type of mutations in a specific sequence define a mutational spectrum. When all tumor p53 mutations are grouped together, they identify several codons with high mutation frequencies (hot spots). When examined separately by cancer type, clear differences in spectra emerge, both in the position of hot spots and in the frequency of transitions and transversions. For example, colon and breast cancers have different mutation patterns. G:C to A:T transitions are the majority in colon tumors, while G to T transversions are rare in colorectal cancer but common in breast tumors. Lymphomas and leukemias have similar mutation patterns to colorectal tumors, with CpG dinucleotide transitions being a major fraction of point mutations.