From polyploidy to aneuploidy, genome instability and cancer View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2004-01

AUTHORS

Zuzana Storchova, David Pellman

ABSTRACT

Key PointsPolyploidy is a relatively common event in eukaryotic organisms. Polyploid cells can arise during development by cell fusion, endoreplication or an abortive cell cycle. There is also evidence that polyploid cells might form more frequently during ageing or stress.The physiology of polyploids is altered relative to diploids: there are alterations in gene expression and genetic stability, and certain genes that are not essential for viability in diploid yeasts become essential in polyploid yeast, a phenomenon known as ploidy-specific lethality.Increased ploidy in animal cells usually results in a proportional increase in the number of centrosomes. The presence of supernumerary centrosomes can lead to: i) cell-cycle arrest by a recently described tetraploidy checkpoint; ii) apoptosis; iii) a return to a diploid state through a poorly characterized process that is known as a reduction mitosis; or iv) successful propagation after an adaptation that allows the clustering of extra centrosomes.Tumour cells frequently have an increased number of aberrant chromosomes (aneuploidy) and extra centrosomes.It is generally assumed that aneuploidy develops from diploid cells by ongoing chromosomal instability. In light of recent studies on the tetraploidy checkpoint, and because of the need to explain why tumours often have extra centrosomes, we reconsider an old hypothesis about the genesis of aneuploidy: that aneuploidy can develop in cells after an abortive cell cycle that forces cells through a tetraploid intermediate. Furthermore, we consider the possibility that the altered physiology of cells with extra chromosomes, particularly the phenomenon of ploidy-specific lethality, could be exploited to develop new drugs that selectively kill cancer cells but not normal cells. More... »

PAGES

45-54

References to SciGraph publications

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    74 diploid yeast
    75 drugs
    76 endoreplication
    77 eukaryotic organisms
    78 events
    79 evidence
    80 expression
    81 extra centrosomes
    82 extra chromosome
    83 fusion
    84 gene expression
    85 genes
    86 genesis
    87 genesis of aneuploidy
    88 genetic stability
    89 genome instability
    90 hypothesis
    91 increase
    92 instability
    93 lethality
    94 light
    95 mitosis
    96 need
    97 new drugs
    98 normal cells
    99 number
    100 number of centrosomes
    101 old hypothesis
    102 ongoing chromosomal instability
    103 organisms
    104 phenomenon
    105 physiology
    106 polyploid cells
    107 polyploid yeast
    108 polyploids
    109 polyploidy
    110 possibility
    111 presence
    112 process
    113 propagation
    114 proportional increase
    115 return
    116 stability
    117 state
    118 stress
    119 study
    120 successful propagation
    121 supernumerary centrosomes
    122 tetraploid
    123 tetraploidy checkpoint
    124 tumor cells
    125 tumors
    126 viability
    127 yeast
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