The roles of telomerase in the generation of polyploidy during neoplastic cell growth

Agni Christodoulidou, Christina Raftopoulou, Maria Chiourea, George K. Papaioannou, Hirotoshi Hoshiyama, Woodring E. Wright, Jerry W. Shay, Sarantis Gagos

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Polyploidy contributes to extensive intratumor genomic heterogeneity that characterizes advanced malignancies and is thought to limit the efficiency of current cancer therapies. It has been shown that telomere deprotection in p53-deficient mouse embryonic fibroblasts leads to high rates of polyploidization. We now show that tumor genome evolution through whole-genome duplication occurs in ~15% of the karyotyped human neoplasms and correlates with disease progression. In a panel of human cancer and transformed cell lines representing the two known types of genomic instability (chromosomal and microsatellite), as well as the two known pathways of telomere maintenance in cancer (telomerase activity and alternative lengthening of telomeres), telomere dysfunction-driven polyploidization occurred independently of the mutational status of p53. Depending on the preexisting context of telomere maintenance, telomerase activity and its major components, human telomerase reverse transcriptase (hTERT) and human telomerase RNA component (hTERC), exert both reverse transcriptase-related (canonical) and noncanonical functions to affect tumor genome evolution through suppression or induction of polyploidization. These new findings provide a more complete mechanistic understanding of cancer progression that may, in the future, lead to novel therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)156-168
Number of pages13
JournalNeoplasia (United States)
Volume15
Issue number2
DOIs
StatePublished - Feb 2013

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Polyploidy
Telomerase
Telomere
Growth
Neoplasms
Genome
Telomere Homeostasis
Maintenance
Transformed Cell Line
Genomic Instability
RNA-Directed DNA Polymerase
Microsatellite Repeats
Disease Progression
Fibroblasts
Therapeutics

ASJC Scopus subject areas

  • Cancer Research

Cite this

Christodoulidou, A., Raftopoulou, C., Chiourea, M., Papaioannou, G. K., Hoshiyama, H., Wright, W. E., ... Gagos, S. (2013). The roles of telomerase in the generation of polyploidy during neoplastic cell growth. Neoplasia (United States), 15(2), 156-168. https://doi.org/10.1593/neo.121398

The roles of telomerase in the generation of polyploidy during neoplastic cell growth. / Christodoulidou, Agni; Raftopoulou, Christina; Chiourea, Maria; Papaioannou, George K.; Hoshiyama, Hirotoshi; Wright, Woodring E.; Shay, Jerry W.; Gagos, Sarantis.

In: Neoplasia (United States), Vol. 15, No. 2, 02.2013, p. 156-168.

Research output: Contribution to journalArticle

Christodoulidou, A, Raftopoulou, C, Chiourea, M, Papaioannou, GK, Hoshiyama, H, Wright, WE, Shay, JW & Gagos, S 2013, 'The roles of telomerase in the generation of polyploidy during neoplastic cell growth', Neoplasia (United States), vol. 15, no. 2, pp. 156-168. https://doi.org/10.1593/neo.121398
Christodoulidou A, Raftopoulou C, Chiourea M, Papaioannou GK, Hoshiyama H, Wright WE et al. The roles of telomerase in the generation of polyploidy during neoplastic cell growth. Neoplasia (United States). 2013 Feb;15(2):156-168. https://doi.org/10.1593/neo.121398
Christodoulidou, Agni ; Raftopoulou, Christina ; Chiourea, Maria ; Papaioannou, George K. ; Hoshiyama, Hirotoshi ; Wright, Woodring E. ; Shay, Jerry W. ; Gagos, Sarantis. / The roles of telomerase in the generation of polyploidy during neoplastic cell growth. In: Neoplasia (United States). 2013 ; Vol. 15, No. 2. pp. 156-168.
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