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[Cancer Research 64, 2324-2327, April 1, 2004]
© 2004 American Association for Cancer Research

Advances In Brief

Alternative Lengthening of Telomeres Is Characterized by High Rates of Telomeric Exchange

J. Arturo Londoño-Vallejo1, Héra Der-Sarkissian2, Lucien Cazes2, Silvia Bacchetti3 and Roger R. Reddel4

1 Institut National de la Santé et de la Recherche Médicale, Paris, France; 2 Centre d’Etude du Polymorphisme Humain, Paris, France; 3 Laboratorio di Oncogenesi Molecolare, Istituto Regina Elena, Roma, Italy; and 4 Cancer Research Unit, Children’s Medical Research Institute, Westmead, New South Wales, Australia

Telomere maintenance activity is a hallmark of cancer. In some telomerase-negative tumors, telomeres become lengthened by alternative lengthening of telomeres (ALT), a recombination-mediated DNA replication process in which telomeres use other telomeric DNA as a copy template. Using chromosome orientation fluorescence in situ hybridization, we found that postreplicative exchange events involving a telomere and another TTAGGG-repeat tract occur at remarkably high frequencies in ALT cells (range 28–280/100 metaphases) and rarely or never in non-ALT cells, including cell lines with very long telomeres. Like the ALT phenotype itself, the telomeric exchanges were not suppressed when telomerase was activated in ALT cells. These exchanges are telomere specific because there was no correlation with sister chromatid exchange rates at interstitial locations, and they were not observed in non-ALT Bloom syndrome cells with very high sister chromatid exchange rates.




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