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Title

Pericentromeric instability and spontaneous emergence of human neoacrocentric and minute chromosomes in the alternative pathway of telomere lengthening

Authors
Chiourea, Maria
Christodoulidou, Agni
Apostolou, Eftichia
Raftopoulou, Christina
Deustch, Samuel
Jefford, C. E.
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Published in Cancer Research. 2008, vol. 68, no. 19, p. 8146-8155
Abstract In the alternative pathway of telomere lengthening (ALT), neoplastic cell growth is prolonged by telomere recombination. We show that ALT is unexpectedly characterized by high rates of ongoing pericentromeric chromosomal instability. Combined with telomeric recombination, ALT pericentromeric instability generates neoacrocentric chromosomes. In the present studies, we describe a subgroup of ALT neoacrocentric minute chromosomes, composed of DNA entities two to five times smaller in size than human chromosome 21. The frequencies of ALT minute chromosomes were increased by gamma-irradiation and suppressed by telomerase. Continuous growth after telomerase inhibition/depletion was followed by increased rates of telomeric sister chromatid recombination and the emergence of minute chromosomes. We show that ALT minute chromosomes were derived from true centromeric fissions and/or chromosomal breakage/fusion/bridge cycles. They exhibit a two-chromatid structure, carry genomic DNA, centromeric and telomeric repeats, and display regular mitotic functionality. These observations are important in understanding the global genomic instability that characterizes most human advanced malignancies.
Keywords Cell ProliferationCentromere/genetics/ultrastructureChromosomal Instability/ physiologyChromosome AberrationsChromosome BreakageCytogenetic AnalysisHCT116 CellsHT29 CellsHela CellsHumansSignal Transduction/ genetics/physiologyTelomerase/physiologyTelomere/ physiologyTumor Cells, Cultured
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PMID: 18829574
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GAGOS, Sarantis et al. Pericentromeric instability and spontaneous emergence of human neoacrocentric and minute chromosomes in the alternative pathway of telomere lengthening. In: Cancer Research, 2008, vol. 68, n° 19, p. 8146-8155. https://archive-ouverte.unige.ch/unige:8748

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Deposited on : 2010-07-12

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