{"entity":{"id":"paper-hollstein-p53-mutations-science-1991","kind":"paper","name":"Hollstein 1991: p53 mutations in human cancers","aka":[],"tldr":"The survey that showed p53 is the most commonly altered gene in human cancer and that the pattern of its mutations differs by cancer type and by cause, such as tobacco smoke in lung cancer and a dietary toxin in liver cancer.","summary":"Hollstein, Sidransky, Vogelstein and Harris compiled the p53 mutations reported across human tumours and showed that they occurred in a wide range of cancers, clustered in the evolutionarily conserved regions of the gene, and mostly changed single amino acids rather than truncating the protein. The spectrum of mutations varied by tumour type and exposure: G to T changes typical of tobacco carcinogens in lung cancer and a specific codon 249 change in liver cancers from regions with aflatoxin exposure. The paper established p53 mutation as a molecular record of carcinogen exposure.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1126/science.1905840"}],"tags":[],"related":[],"cancers":["nsclc","hcc","colorectal"],"sections":[],"technologies":[],"targets":["tp53"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["tp53-mutated","tumour-suppressor-gene","mutational-signature"],"trials":[],"people":["bert-vogelstein"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Science","year":1991,"doi":"10.1126/science.1905840","authors":"Hollstein M, Sidransky D, Vogelstein B, Harris CC.","paperType":"review","findings":["p53 mutations were found across a wide range of human cancers, making it the most frequently mutated gene known.","Mutations clustered in four conserved regions of the gene and were mostly missense changes.","Mutation spectra differed by cancer and exposure, including tobacco-associated changes in lung cancer and a codon 249 hotspot in aflatoxin-related liver cancer."],"whatItMeans":"This paper is why TP53 status is reported in almost every tumour genome and why mutational signatures can point to causes. Its idea that mutation patterns record exposures grew into the mutational signature field, and TP53 mutation remains a marker of shorter survival and a drug target still being pursued.","caveats":["A compilation of early sequencing studies with uneven coverage across cancers.","The functional consequences of different p53 mutations were still largely unknown."],"changedPractice":false},"route":"/key-papers/paper-hollstein-p53-mutations-science-1991/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"target":[{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"institution":[{"id":"johns-hopkins","kind":"institution","name":"Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center","route":"/institutions/johns-hopkins/"}],"term":[{"id":"mutational-signature","kind":"term","name":"Mutational signature","route":"/terms/mutational-signature/"},{"id":"tp53-mutated","kind":"term","name":"TP53-mutated (p53-abnormal)","route":"/terms/tp53-mutated/"},{"id":"tumour-suppressor-gene","kind":"term","name":"Tumour suppressor gene","route":"/terms/tumour-suppressor-gene/"}],"person":[{"id":"bert-vogelstein","kind":"person","name":"Bert Vogelstein","route":"/people/bert-vogelstein/"}],"paper":[{"id":"paper-levine-p53-gatekeeper-cell-1997","kind":"paper","name":"Levine 1997: p53, the cellular gatekeeper for growth and division","route":"/key-papers/paper-levine-p53-gatekeeper-cell-1997/"},{"id":"paper-vogelstein-surfing-p53-network-nature-2000","kind":"paper","name":"Vogelstein, Lane and Levine 2000: surfing the p53 network","route":"/key-papers/paper-vogelstein-surfing-p53-network-nature-2000/"}]}}