Home LiteratureArticle Details
PMID: 17974949 Published · ppublish English Journal Article Review

Aneuploidy: instigator and inhibitor of tumorigenesis.

Cancer research ·Vol. 67 ·No. 21 ·2007-11-01 ·Pages 10103-5

Weaver BA, Cleveland DW

Abstract

Aneuploidy, an aberrant chromosome number, has been recognized as a common characteristic of cancer cells for more than 100 years and has been suggested as a cause of tumorigenesis for nearly as long. However, this proposal had remained untested due to the difficulty of selectively generating aneuploidy without causing other damage. Using Cenp-E heterozygous animals, which develop whole chromosome aneuploidy in the absence of other defects, we have found that aneuploidy promotes tumorigenesis in some contexts and inhibits it in others. These findings confirm that aneuploidy can act oncogenically and reveal a previously unsuspected role for aneuploidy as a tumor suppressor.

MeSH Terms
Aneuploidy Animals Calcium-Binding Proteins/physiology Cell Cycle Proteins/physiology Chromosomal Proteins, Non-Histone/analysis,genetics Chromosome Segregation DNA Damage Humans Mad2 Proteins Neoplasms/genetics,prevention & control Repressor Proteins/physiology
Chemicals
Calcium-Binding Proteins Cell Cycle Proteins Chromosomal Proteins, Non-Histone MAD2L1 protein, human Mad2 Proteins Repressor Proteins centromere protein E
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Weaver Beth A A
Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093-0670, USA.
Cleveland Don W
References (33)
33 references, click to expand
  1. Which came first? Studies clarify role of aneuploidy in cancer.
    J Natl Cancer Inst. 2005 Jan 19;97(2):87-9 PMID: 15657335
  2. Complete loss of the tumor suppressor MAD2 causes premature cyclin B degradation and mitotic failure in human somatic cells.
    Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4459-64 PMID: 15070740
  3. Early aging-associated phenotypes in Bub3/Rae1 haploinsufficient mice.
    J Cell Biol. 2006 Feb 13;172(4):529-40 PMID: 16476774
  4. DNA replication checkpoint control mediated by the spindle checkpoint protein Mad2p in fission yeast.
    J Biol Chem. 2004 Nov 5;279(45):47372-8 PMID: 15347659
  5. Lethality to human cancer cells through massive chromosome loss by inhibition of the mitotic checkpoint.
    Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8699-704 PMID: 15159543
  6. Rae1 is an essential mitotic checkpoint regulator that cooperates with Bub3 to prevent chromosome missegregation.
    J Cell Biol. 2003 Feb 3;160(3):341-53 PMID: 12551952
  7. Rb inactivation promotes genomic instability by uncoupling cell cycle progression from mitotic control.
    Nature. 2004 Aug 12;430(7001):797-802 PMID: 15306814
  8. BUBR1 deficiency results in abnormal megakaryopoiesis.
    Blood. 2004 Feb 15;103(4):1278-85 PMID: 14576056
  9. Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies.
    BMJ. 2000 Aug 5;321(7257):323-9 PMID: 10926586
  10. BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice.
    Nat Genet. 2004 Jul;36(7):744-9 PMID: 15208629
  11. A mutator phenotype in cancer.
    Cancer Res. 2001 Apr 15;61(8):3230-9 PMID: 11309271
  12. Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection.
    Proc Natl Acad Sci U S A. 1973 Aug;70(8):2281-5 PMID: 4151811
  13. WD repeat-containing mitotic checkpoint proteins act as transcriptional repressors during interphase.
    FEBS Lett. 2004 Sep 24;575(1-3):23-9 PMID: 15388328
  14. Does aneuploidy cause cancer?
    Curr Opin Cell Biol. 2006 Dec;18(6):658-67 PMID: 17046232
  15. Unstable kinetochore-microtubule capture and chromosomal instability following deletion of CENP-E.
    Dev Cell. 2002 Sep;3(3):351-65 PMID: 12361599
  16. The yeast nuclear pore complex functionally interacts with components of the spindle assembly checkpoint.
    J Cell Biol. 2002 Dec 9;159(5):807-19 PMID: 12473689
  17. Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss.
    J Cell Biol. 2003 Aug 18;162(4):551-63 PMID: 12925705
  18. Dual roles of human BubR1, a mitotic checkpoint kinase, in the monitoring of chromosomal instability.
    Cancer Cell. 2003 Dec;4(6):483-97 PMID: 14706340
  19. Genomic changes defining the genesis, progression, and malignancy potential in solid human tumors: a phenotype/genotype correlation.
    Genes Chromosomes Cancer. 1999 Jul;25(3):195-204 PMID: 10379865
  20. Mitotic checkpoint proteins HsMAD1 and HsMAD2 are associated with nuclear pore complexes in interphase.
    J Cell Sci. 2001 Mar;114(Pt 5):953-63 PMID: 11181178
  21. Aneuploidy acts both oncogenically and as a tumor suppressor.
    Cancer Cell. 2007 Jan;11(1):25-36 PMID: 17189716
  22. Primary vs. secondary neoplasia-associated chromosomal abnormalities--balanced rearrangements vs. genomic imbalances?
    Genes Chromosomes Cancer. 1996 Jul;16(3):155-63 PMID: 8814447
  23. Cyclin-like accumulation and loss of the putative kinetochore motor CENP-E results from coupling continuous synthesis with specific degradation at the end of mitosis.
    J Cell Biol. 1994 Jun;125(6):1303-12 PMID: 8207059
  24. BubR1 is involved in regulation of DNA damage responses.
    Oncogene. 2006 Jun 15;25(25):3598-605 PMID: 16449973
  25. Increased chromosome instability but not cancer predisposition in haploinsufficient Bub3 mice.
    Genes Chromosomes Cancer. 2005 Sep;44(1):29-36 PMID: 15898111
  26. Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients.
    Nat Med. 1996 Feb;2(2):169-74 PMID: 8574961
  27. Aneuploidy and cancer: from correlation to causation.
    Contrib Microbiol. 2006;13:16-44 PMID: 16627957
  28. Derivation of human tumor cells in vitro without widespread genomic instability.
    Cancer Res. 2001 Dec 15;61(24):8838-44 PMID: 11751406
  29. Mad2 overexpression promotes aneuploidy and tumorigenesis in mice.
    Cancer Cell. 2007 Jan;11(1):9-23 PMID: 17189715
  30. MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells.
    Nature. 2001 Jan 18;409(6818):355-9 PMID: 11201745
  31. Chromosome nondisjunction yields tetraploid rather than aneuploid cells in human cell lines.
    Nature. 2005 Oct 13;437(7061):1038-42 PMID: 16222248
  32. Mitotic checkpoint function in the formation of gross chromosomal rearrangements in Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15980-5 PMID: 15514023
  33. Aneuploidy correlated 100% with chemical transformation of Chinese hamster cells.
    Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14506-11 PMID: 9405643
Article Info
Journal
Cancer research
Abbr.
Cancer Res
ISSN
1538-7445
DOI
10.1158/0008-5472.CAN-07-2266
Published
2007-11-01
Pages
10103-5
Language
English
Region
United States
NLM ID
2984705R
PMCID
PMC3132555
Subset
IM
Grants
NIGMS NIH HHS · R01 GM029513 · United States
NIGMS NIH HHS · R01 GM029513-25 · United States
NIGMS NIH HHS · R01 GM029513-26 · United States
External Links
PubMed source DOI: 10.1158/0008-5472.CAN-07-2266 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2