Cited by 8,018Cancer-related Molecular PathwaysCancer Genomics and DiagnosticsGenetic factors in colorectal cancer

p53 Mutations in Human Cancers

Hollstein, Monica, Sidransky, David, Vogelstein, Bert, Harris, Curtis C.·1991·Science

Abstract

Mutations in the evolutionarily conserved codons of the p53 tumor suppressor gene are common in diverse types of human cancer. The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hemopoietic tissues. Analysis of these mutations can provide clues to the etiology of these diverse tumors and to the function of specific regions of p53. Transitions predominate in colon, brain, and lymphoid malignancies, whereas G:C to T:A transversions are the most frequent substitutions observed in cancers of the lung and liver. Mutations at A:T base pairs are seen more frequently in esophageal carcinomas than in other solid tumors. Most transitions in colorectal carcinomas, brain tumors, leukemias, and lymphomas are at CpG dinucleotide mutational hot spots. G to T transversions in lung, breast, and esophageal carcinomas are dispersed among numerous codons. In liver tumors in persons from geographic areas in which both aflatoxin B 1 and hepatitis B virus are cancer risk factors, most mutations are at one nucleotide pair of codon 249. These differences may reflect the etiological contributions of both exogenous and endogenous factors to human carcinogenesis.

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Crossref · 10.1126/science.1905840

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Authors
Hollstein, M., Sidransky, D., Vogelstein, B., & Harris, C. C.
Affiliations
  • National Institutes of Health (US)
  • Johns Hopkins University (US)
Venue
Science
Published
1991-07-05
Volume
253
Issue
5015
Pages
49-53
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2042316019
Cited by
8,018
References
84
Citations by year
2026: 24 · 2025: 53 · 2024: 69 · 2023: 98 · 2022: 114 · 2021: 124 · 2020: 120 · 2019: 121 · 2018: 123 · 2017: 144 · 2016: 152 · 2015: 172 · 2014: 222 · 2013: 208 · 2012: 214
FWCI
182.58
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (CA 09071, CA43460, T32CA009071)
Topics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords
p53, TP53 mutation, tumor suppressor, mutation spectrum, transitions and transversions, colorectal cancer, lung cancer, esophageal cancer, breast cancer, liver cancer, brain tumors, leukemia, lymphoma, aflatoxin B1, hepatitis B virus, carcinogenesis
MeSH terms
Amino Acid Sequence, Animals, Haplorhini, Base Sequence, Chickens, DNA Mutational Analysis, Humans, Molecular Sequence Data, Mutation, Neoplasms, Sequence Homology, Nucleic Acid, Trout, Xenopus, Genes, p53, Mice, Rats

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