Movatterモバイル変換

[0]ホーム
URL:

Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

Atypon full text link Atypon Free PMC article
Full text links

Actions

Share

.2000 Mar 28;97(7):3236-41.
doi: 10.1073/pnas.97.7.3236.

Aneuploidy vs. gene mutation hypothesis of cancer: recent study claims mutation but is found to support aneuploidy

Affiliations

Aneuploidy vs. gene mutation hypothesis of cancer: recent study claims mutation but is found to support aneuploidy

R Li et al. Proc Natl Acad Sci U S A..

Abstract

For nearly a century, cancer has been blamed on somatic mutation. But it is still unclear whether this mutation is aneuploidy, an abnormal balance of chromosomes, or gene mutation. Despite enormous efforts, the currently popular gene mutation hypothesis has failed to identify cancer-specific mutations with transforming function and cannot explain why cancer occurs only many months to decades after mutation by carcinogens and why solid cancers are aneuploid, although conventional mutation does not depend on karyotype alteration. A recent high-profile publication now claims to have solved these discrepancies with a set of three synthetic mutant genes that "suffices to convert normal human cells into tumorigenic cells." However, we show here that even this study failed to explain why it took more than "60 population doublings" from the introduction of the first of these genes, a derivative of the tumor antigen of simian virus 40 tumor virus, to generate tumor cells, why the tumor cells were clonal although gene transfer was polyclonal, and above all, why the tumor cells were aneuploid. If aneuploidy is assumed to be the somatic mutation that causes cancer, all these results can be explained. The aneuploidy hypothesis predicts the long latent periods and the clonality on the basis of the following two-stage mechanism: stage one, a carcinogen (or mutant gene) generates aneuploidy; stage two, aneuploidy destabilizes the karyotype and thus initiates an autocatalytic karyotype evolution generating preneoplastic and eventually neoplastic karyotypes. Because the odds are very low that an abnormal karyotype will surpass the viability of a normal diploid cell, the evolution of a neoplastic cell species is slow and thus clonal, which is comparable to conventional evolution of new species.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The chromosomes of a representative aneuploid cell of the tumorigenic human HA1 ER (a) and BJ ELR (b) cell lines. Metaphase chromosomes of these cells were prepared as described previously (51) and photographed ×630 after Giemsa staining. The HA1 ER metaphase shown contains 78 and the BJ ELR metaphase contains 82 chromosomes.
Figure 2
Figure 2
A two-stage model for how carcinogens may cause cancer via aneuploidy. Stage one: a carcinogen “initiates” carcinogenesis by generating an aneuploid cell. Stage two: aneuploidy destabilizes symmetric chromosome segregation, because it unbalances spindle and chromosomal proteins and centrosome numbers by unbalancing their chromosomal templates (see text). As a result, aneuploidy initiates autocatalytic karyotype variation and evolution, which generates new lethal, preneoplastic and eventually neoplastic karyotypes. The autocatalytic karyotype evolution would explain the previously unresolved carcinogen-independent transformation of an “initiated” preneoplastic into a neoplastic cell (8, 9, 62). The notorious long latent periods from initiation to carcinogenesis would be a consequence of the low probability of generating by chance a karyotype that can outperform normal cells. Autocatalytic karyotype variation would also explain the notorious genetic instability and phenotypic heterogeneity of cancer cells (9, 43).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Tyzzer E E. J Cancer Res. 1916;1:125–155.
    1. Strong L C. Br J Cancer. 1949;3:97–108. - PMC - PubMed
    1. Kacser H, Burns J A. Genetics. 1981;97:639–666. - PMC - PubMed
    1. Cornish-Bowden A. In: Biotechnology. Rehm H-J, Reed G, editors. New York: VCH; 1995. pp. 121–136.
    1. Yosida T H. Cancer Genet Cytogenet. 1983;8:153–179. - PubMed

Publication types

MeSH terms

Related information

LinkOut - more resources

Full text links
Atypon full text link Atypon Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

[8]ページ先頭
©2009-2025 Movatter.jp