Divergent patterns of telomere maintenance mechanisms among human sarcomas

Sharply contrasting prevalence of the alternative lengthening of telomeres mechanism in Ewing's sarcomas and osteosarcomas

Gary A. Ulaner, Andrew R. Hoffman, Jesse Otero, Hsuan Ying Huang, Zhiquan Zhao, Madhu Mazumdar, Richard Gorlick, Paul Meyers, John H. Healey, Marc Ladanyi

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Two types of telomere maintenance mechanisms (TMMs) have been described in human tumors: telomerase activation and alternative lengthening of telomeres (ALT). Although the vast majority of epithelial tumors rely on telomerase activation, many mesenchymal tumors rely on ALT for telomere maintenance, but within this tumor group, the TMMs used by translocation-associated sarcomas have not been systematically studied. We studied telomere lengths and telomerase expression and activity in 30 uncultured tumor samples and in 10 cell lines of Ewing's sarcoma, a prototypical translocation-associated sarcoma, and compared the data to an identical analysis of 60 osteosarcomas, the most common type of sarcoma lacking a specific translocation. Telomerase activity was demonstrated in 21 Ewing's sarcoma tumor samples (70%) and in 9 of 10 Ewing's sarcoma cell lines. Evidence of ALT, indicated by the presence of long and heterogeneous telomeres, was observed only in the cell line without telomerase activity and in none of the 30 Ewing's sarcoma tumor samples. The 9 Ewing's sarcoma patients whose tumors lacked detectable telomerase activity did not differ significantly from the remaining patients in age, stage, EWSRI-FLII fusion type, prevalence of TP53 point mutations, or overall survival. The low prevalence of ALT in Ewing's sarcoma contrasted sharply with our data on TMMs in 60 osteosarcomas, which showed ALT in 38 of 60 cases (P < 0.0001). The present study, together with emerging published data on other sarcoma types, suggests that a predominance of telomerase activation in the absence of ALT may characterize sarcomas with specific chromosomal translocations (such as Ewing's sarcoma), whereas a high prevalence of ALT appears typical of sarcomas with nonspecific complex karyotypes (such as osteosarcoma).

Original languageEnglish (US)
Pages (from-to)155-162
Number of pages8
JournalGenes Chromosomes and Cancer
Volume41
Issue number2
DOIs
StatePublished - Oct 2004
Externally publishedYes

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Telomere Homeostasis
Ewing's Sarcoma
Telomere
Osteosarcoma
Sarcoma
Telomerase
Maintenance
Neoplasms
Cell Line
Genetic Translocation
Karyotype
Point Mutation

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Divergent patterns of telomere maintenance mechanisms among human sarcomas : Sharply contrasting prevalence of the alternative lengthening of telomeres mechanism in Ewing's sarcomas and osteosarcomas. / Ulaner, Gary A.; Hoffman, Andrew R.; Otero, Jesse; Huang, Hsuan Ying; Zhao, Zhiquan; Mazumdar, Madhu; Gorlick, Richard; Meyers, Paul; Healey, John H.; Ladanyi, Marc.

In: Genes Chromosomes and Cancer, Vol. 41, No. 2, 10.2004, p. 155-162.

Research output: Contribution to journalArticle

Ulaner, Gary A. ; Hoffman, Andrew R. ; Otero, Jesse ; Huang, Hsuan Ying ; Zhao, Zhiquan ; Mazumdar, Madhu ; Gorlick, Richard ; Meyers, Paul ; Healey, John H. ; Ladanyi, Marc. / Divergent patterns of telomere maintenance mechanisms among human sarcomas : Sharply contrasting prevalence of the alternative lengthening of telomeres mechanism in Ewing's sarcomas and osteosarcomas. In: Genes Chromosomes and Cancer. 2004 ; Vol. 41, No. 2. pp. 155-162.
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abstract = "Two types of telomere maintenance mechanisms (TMMs) have been described in human tumors: telomerase activation and alternative lengthening of telomeres (ALT). Although the vast majority of epithelial tumors rely on telomerase activation, many mesenchymal tumors rely on ALT for telomere maintenance, but within this tumor group, the TMMs used by translocation-associated sarcomas have not been systematically studied. We studied telomere lengths and telomerase expression and activity in 30 uncultured tumor samples and in 10 cell lines of Ewing's sarcoma, a prototypical translocation-associated sarcoma, and compared the data to an identical analysis of 60 osteosarcomas, the most common type of sarcoma lacking a specific translocation. Telomerase activity was demonstrated in 21 Ewing's sarcoma tumor samples (70{\%}) and in 9 of 10 Ewing's sarcoma cell lines. Evidence of ALT, indicated by the presence of long and heterogeneous telomeres, was observed only in the cell line without telomerase activity and in none of the 30 Ewing's sarcoma tumor samples. The 9 Ewing's sarcoma patients whose tumors lacked detectable telomerase activity did not differ significantly from the remaining patients in age, stage, EWSRI-FLII fusion type, prevalence of TP53 point mutations, or overall survival. The low prevalence of ALT in Ewing's sarcoma contrasted sharply with our data on TMMs in 60 osteosarcomas, which showed ALT in 38 of 60 cases (P < 0.0001). The present study, together with emerging published data on other sarcoma types, suggests that a predominance of telomerase activation in the absence of ALT may characterize sarcomas with specific chromosomal translocations (such as Ewing's sarcoma), whereas a high prevalence of ALT appears typical of sarcomas with nonspecific complex karyotypes (such as osteosarcoma).",
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