# Genetic instability of cancer cells is proportional to their degree of aneuploidy

Source: https://onco.cc/key-papers/paper-duesberg-proc-natl-acad-sci-u-s-a/  
OnCo record `paper-duesberg-proc-natl-acad-sci-u-s-a` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Paper cited by one term page, indexed on Europe PMC as PubMed record 9811862 and published in Proceedings of the National Academy of Sciences; the citing page links this DOI, which is how the record was matched.

## Summary

Genetic and phenotypic instability are hallmarks of cancer cells, but their cause is not clear. The leading hypothesis suggests that a poorly defined gene mutation generates genetic instability and that some of many subsequent mutations then cause cancer. Here we investigate the hypothesis that genetic instability of cancer cells is caused by aneuploidy, an abnormal balance of chromosomes. Because symmetrical segregation of chromosomes depends on exactly two copies of mitosis genes, aneuploidy involving chromosomes with mitosis genes will destabilize the karyotype. The hypothesis predicts that the degree of genetic instability should be proportional to the degree of aneuploidy. Thus it should be difficult, if not impossible, to maintain the particular karyotype of a highly aneuploid cancer cell on clonal propagation. This prediction was confirmed with clonal cultures of chemically transformed, aneuploid Chinese hamster embryo cells. It was found that the higher the ploidy factor of a clone, the more unstable was its karyotype. The ploidy factor is the quotient of the modal chromosome number divided by the normal number of the species. Transformed Chinese hamster embryo cells with a ploidy factor of 1.7 were estimated to change their karyotype at a rate of about 3% per generation, compared with 1.8% for cells with a ploidy factor of 0.95. Because the background noise of karyotyping is relatively high, the cells with low ploidy factor may be more stable than our method suggests. The karyotype instability of human colon cancer cell lines, recently analyzed by Lengnauer et al. [Lengnauer, C., Kinzler, K. W. & Vogelstein, B. (1997) Nature (London) 386, 623-627], also corresponds exactly to their degree of aneuploidy. We conclude that aneuploidy is sufficient to explain genetic instability and the resulting karyotypic and phenotypic heterogeneity of cancer cells, independent of gene mutation. Because aneuploidy has also been proposed to cause cancer, our hypothesis offers a common, unique mechanism of altering and simultaneously destabilizing normal cellular phenotypes.

Indexed on Europe PMC as PubMed record 9811862 (DOI 10.1073/pnas.95.23.13692). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Proceedings of the National Academy of Sciences
- Year: 1998
- DOI: 10.1073/pnas.95.23.13692
- Authors: Duesberg P, Rausch C, Rasnick D, et al.
- What it means: One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
- Caveats: Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper.

## Sources

- Proc Natl Acad Sci U S A 1998: https://doi.org/10.1073/pnas.95.23.13692
- PubMed: https://pubmed.ncbi.nlm.nih.gov/9811862/
- Europe PMC: https://europepmc.org/article/MED/9811862

## Connected records

- terms: [Aneuploidy and chromosomal instability as the cause of cancer](https://onco.cc/terms/aneuploidy-theory-of-cancer/)
- journals: [Proceedings of the National Academy of Sciences](https://onco.cc/journals/pnas/)

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