From polyploidy to aneuploidy, genome instability and cancer

Polyploidy is a frequent phenomenon in the eukaryotic world, but the biological properties of polyploid cells are not well understood. During evolution, polyploidy is thought to be an important mechanism that contributes to speciation. Polyploid, usually non-dividing, cells are formed during develop...

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Published inNature reviews. Molecular cell biology Vol. 5; no. 1; pp. 45 - 54
Main Authors Pellman, David, Storchova, Zuzana
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 01.01.2004
Subjects
Aneuploidy
Animals
Biological Evolution
Cancer
Cell cycle
Cell division
Chromosomes
Evolution
Genomes
Genomic Instability - genetics
Humans
Insects
Models, Genetic
Neoplasms - genetics
Oncology
Organisms
Pediatrics
Polyploidy
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Abstract Polyploidy is a frequent phenomenon in the eukaryotic world, but the biological properties of polyploid cells are not well understood. During evolution, polyploidy is thought to be an important mechanism that contributes to speciation. Polyploid, usually non-dividing, cells are formed during development in otherwise diploid organisms. A growing amount of evidence indicates that polyploid cells also arise during a variety of pathological conditions. Genetic instability in these cells might provide a route to aneuploidy and thereby contribute to the development of cancer.
AbstractList Polyploidy is a frequent phenomenon in the eukaryotic world, but the biological properties of polyploid cells are not well understood. During evolution, polyploidy is thought to be an important mechanism that contributes to speciation. Polyploid, usually non-dividing, cells are formed during development in otherwise diploid organisms. A growing amount of evidence indicates that polyploid cells also arise during a variety of pathological conditions. Genetic instability in these cells might provide a route to aneuploidy and thereby contribute to the development of cancer.
Polyploidy is a frequent phenomenon in the eukaryotic world, but the biological properties of polyploid cells are not well understood. During evolution, polyploidy is thought to be an important mechanism that contributes to speciation. Polyploid, usually non-dividing, cells are formed during development in otherwise diploid organisms. A growing amount of evidence indicates that polyploid cells also arise during a variety of pathological conditions. Genetic instability in these cells might provide a route to aneuploidy and thereby contribute to the development of cancer. In Summary: Polyploidy 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.
Audience Academic
Author Pellman, David
Storchova, Zuzana
Author_xml – sequence: 1
  givenname: David
  surname: Pellman
  fullname: Pellman, David
  organization: Department of Pediatric Oncology of The Dana-Farber Cancer Institute, Department of Pediatric Hematology/Oncology of the Children's Hospital and Harvard Medical School
– sequence: 2
  givenname: Zuzana
  surname: Storchova
  fullname: Storchova, Zuzana
  organization: Department of Pediatric Oncology of The Dana-Farber Cancer Institute, Department of Pediatric Hematology/Oncology of the Children's Hospital and Harvard Medical School
BackLink https://www.ncbi.nlm.nih.gov/pubmed/14708009$$D View this record in MEDLINE/PubMed
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Snippet Polyploidy is a frequent phenomenon in the eukaryotic world, but the biological properties of polyploid cells are not well understood. During evolution,...
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StartPage 45
SubjectTerms Aneuploidy
Animals
Biological Evolution
Cancer
Cell cycle
Cell division
Chromosomes
Evolution
Genomes
Genomic Instability - genetics
Humans
Insects
Models, Genetic
Neoplasms - genetics
Oncology
Organisms
Pediatrics
Polyploidy
Title From polyploidy to aneuploidy, genome instability and cancer
URI http://dx.doi.org/10.1038/nrm1276
https://www.ncbi.nlm.nih.gov/pubmed/14708009
https://www.proquest.com/docview/224673179/abstract/
https://search.proquest.com/docview/19216466
https://search.proquest.com/docview/80082888
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