Mutations of mitotic checkpoint genes in human cancers

Daniel P. Cahill, Christoph Lengauer, Jian Yu, Gregory J. Riggins, James K V Willson, Sanford D. Markowitz, Kenneth W. Kinzler, Bert Vogelstein

Research output: Contribution to journalArticle

1264 Citations (Scopus)

Abstract

Genetic instability was one of the first characteristics to be postulated to underlie neoplasia. Such genetic instability occurs in two different forms. In a small fraction of colorectal and some other cancers, defective repair of mismatched bases results in an increased mutation rate at the nucleotide level and consequent widespread microsatellite instability. In most colorectal cancers, and probably in many other cancer types, a chromosomal instability (CIN) leading to an abnormal chromosome number (aneuploidy) is observed. The physiological and molecular bases of this pervasive abnormality are unknown. Here we show that CIN is consistently associated with the loss of function of a mitotic checkpoint. Moreover, in some cancers displaying CIN the loss of this checkpoint was associated with the mutational inactivation of a human homologue of the yeast BUB1 gene; BUB1 controls mitotic checkpoints and chromosome segregation in yeast. The normal mitotic checkpoints of cells displaying microsatellite instability become defective upon transfer of mutant hBUB1 alleles from either of two CIN cancers.

Original languageEnglish (US)
Pages (from-to)300-303
Number of pages4
JournalNature
Volume392
Issue number6673
DOIs
StatePublished - Mar 19 1998

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M Phase Cell Cycle Checkpoints
Chromosomal Instability
Mutation
Microsatellite Instability
Genes
Neoplasms
Yeasts
Chromosome Segregation
Aneuploidy
Mutation Rate
Colorectal Neoplasms
Nucleotides
Chromosomes
Alleles

ASJC Scopus subject areas

  • General

Cite this

Cahill, D. P., Lengauer, C., Yu, J., Riggins, G. J., Willson, J. K. V., Markowitz, S. D., ... Vogelstein, B. (1998). Mutations of mitotic checkpoint genes in human cancers. Nature, 392(6673), 300-303. https://doi.org/10.1038/32688

Mutations of mitotic checkpoint genes in human cancers. / Cahill, Daniel P.; Lengauer, Christoph; Yu, Jian; Riggins, Gregory J.; Willson, James K V; Markowitz, Sanford D.; Kinzler, Kenneth W.; Vogelstein, Bert.

In: Nature, Vol. 392, No. 6673, 19.03.1998, p. 300-303.

Research output: Contribution to journalArticle

Cahill, DP, Lengauer, C, Yu, J, Riggins, GJ, Willson, JKV, Markowitz, SD, Kinzler, KW & Vogelstein, B 1998, 'Mutations of mitotic checkpoint genes in human cancers', Nature, vol. 392, no. 6673, pp. 300-303. https://doi.org/10.1038/32688
Cahill DP, Lengauer C, Yu J, Riggins GJ, Willson JKV, Markowitz SD et al. Mutations of mitotic checkpoint genes in human cancers. Nature. 1998 Mar 19;392(6673):300-303. https://doi.org/10.1038/32688
Cahill, Daniel P. ; Lengauer, Christoph ; Yu, Jian ; Riggins, Gregory J. ; Willson, James K V ; Markowitz, Sanford D. ; Kinzler, Kenneth W. ; Vogelstein, Bert. / Mutations of mitotic checkpoint genes in human cancers. In: Nature. 1998 ; Vol. 392, No. 6673. pp. 300-303.
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