{"entity":{"id":"paper-lengauer-genetic-instability-colorectal-nature-1997","kind":"paper","name":"Genetic instability in colorectal cancers","aka":[],"tldr":"Colorectal cancers come in two unstable flavours: a few cannot spell-check their DNA, and most cannot divide their chromosomes evenly. This paper measured the second kind for the first time and showed it is a real, continuing defect rather than an accident.","summary":"Colorectal tumours without microsatellite instability were shown to have a striking defect in chromosome segregation, producing gains or losses in excess of 10^-2 per chromosome per generation. The instability reflected a continuing cellular defect that persisted throughout the lifetime of the tumour cell and was not simply a function of chromosome number. Microsatellite instability behaved as a recessive trait in cell fusion experiments, while chromosomal instability behaved as a dominant one. The authors concluded that persistent genetic instability may be necessary for the development of all colorectal cancers and that it arises through two distinct pathways.","asOf":"2026-09-24","links":[{"label":"Lengauer, Kinzler and Vogelstein, Nature 1997: two distinct forms of genetic instability in colorectal cancer","url":"https://doi.org/10.1038/386623a0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9121588/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":["chromosomal-instability","mismatch-repair-msi"],"terms":["msi","copy-number-variation-term"],"trials":[],"people":["bert-vogelstein","kenneth-kinzler"],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":1997,"doi":"10.1038/386623a0","pmid":"9121588","authors":"Lengauer C, Kinzler KW, Vogelstein B.","paperType":"basic","findings":["Chromosome gains or losses above 10^-2 per chromosome per generation in microsatellite-stable lines.","Chromosomal instability is dominant, microsatellite instability recessive, in cell fusions."],"whatItMeans":"It split colorectal cancer into the two instability classes the field still uses, and made the chromosomal class a phenotype to be explained rather than background noise.","caveats":["Cell lines, not tumours in patients.","The molecular cause of chromosomal instability is still not settled."],"changedPractice":false},"route":"/key-papers/paper-lengauer-genetic-instability-colorectal-nature-1997/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"institution":[{"id":"johns-hopkins","kind":"institution","name":"Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center","route":"/institutions/johns-hopkins/"}],"pathway":[{"id":"chromosomal-instability","kind":"pathway","name":"Chromosomal instability & aneuploidy","route":"/pathways/chromosomal-instability/"},{"id":"mismatch-repair-msi","kind":"pathway","name":"Mismatch repair & microsatellite instability","route":"/pathways/mismatch-repair-msi/"}],"term":[{"id":"copy-number-variation-term","kind":"term","name":"Copy number alteration (CNA)","route":"/terms/copy-number-variation-term/"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"}],"person":[{"id":"bert-vogelstein","kind":"person","name":"Bert Vogelstein","route":"/people/bert-vogelstein/"},{"id":"kenneth-kinzler","kind":"person","name":"Kenneth W. Kinzler","route":"/people/kenneth-kinzler/"}],"journal":[{"id":"nature","kind":"journal","name":"Nature","route":"/journals/nature/"}]}}