# Genetic instability in colorectal cancers

Source: https://onco.cc/key-papers/paper-lengauer-genetic-instability-colorectal-nature-1997/  
OnCo record `paper-lengauer-genetic-instability-colorectal-nature-1997` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Nature
- Year: 1997
- DOI: 10.1038/386623a0
- Authors: Lengauer C, Kinzler KW, Vogelstein B.
- 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.
- What it means: 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.

## Sources

- Lengauer, Kinzler and Vogelstein, Nature 1997: two distinct forms of genetic instability in colorectal cancer: https://doi.org/10.1038/386623a0
- PubMed: https://pubmed.ncbi.nlm.nih.gov/9121588/

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- institutions: [Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center](https://onco.cc/institutions/johns-hopkins/)
- pathways: [Chromosomal instability & aneuploidy](https://onco.cc/pathways/chromosomal-instability/), [Mismatch repair & microsatellite instability](https://onco.cc/pathways/mismatch-repair-msi/)
- terms: [Copy number alteration (CNA)](https://onco.cc/terms/copy-number-variation-term/), [Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)](https://onco.cc/terms/msi/)
- people: [Bert Vogelstein](https://onco.cc/people/bert-vogelstein/), [Kenneth W. Kinzler](https://onco.cc/people/kenneth-kinzler/)
- journals: [Nature](https://onco.cc/journals/nature/)

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