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 Journal Article
| Authors: | Ulaner, G. A.; Hoffman, A. R.; Otero, J.; Huang, H. Y.; Zhao, Z.; Mazumdar, M.; Gorlick, R.; Meyers, P.; Healey, J. H.; Ladanyi, M. |
| Article Title: | 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 |
| 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). © 2004 Wiley-Liss, Inc. |
| Keywords: | osteosarcoma; adolescent; adult; child; clinical article; human tissue; bone neoplasms; child, preschool; telomere; gene; reverse transcription polymerase chain reaction; enzyme activity; cell line, tumor; telomerase; ewing sarcoma; sarcoma; infant; reverse transcriptase polymerase chain reaction; chromosome translocation; base sequence; dna primers; point mutation; actins; sarcoma, ewing's; tp53 gene; humans; human; male; female; priority journal; article; htert gene |
| Journal Title: | Genes Chromosomes and Cancer |
| Volume: | 41 |
| Issue: | 2 |
| ISSN: | 1045-2257 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2004-10-01 |
| Start Page: | 155 |
| End Page: | 162 |
| Language: | English |
| DOI: | 10.1002/gcc.20074 |
| PROVIDER: | scopus |
| PUBMED: | 15287028 |
| DOI/URL: | |
| Notes: | Genes Chromosomes Cancer -- Cited By (since 1996):54 -- Export Date: 16 June 2014 -- CODEN: GCCAE -- Source: Scopus |
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