Multiple Mechanisms of Telomere Maintenance Exist in Liposarcomas
| Autor: | Robert J. Varkonyi, Andres J. Klein-Szanto, Dominique Broccoli, Jaclyn Schwalm, Jay E. Johnson, Edna Cukierman, Arthur S. Patchefsky, Ryan Cragle, Margaret von Mehren |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Genome instability Cancer Research Telomerase Biology medicine.disease_cause Recurrence Image Processing Computer-Assisted medicine Humans RNA Messenger Fluorescent Antibody Technique Indirect Peritoneal Neoplasms Aged Cell Proliferation Genetics Mutation Genome Reverse Transcriptase Polymerase Chain Reaction Mechanism (biology) Chromosome Liposarcoma Middle Aged Telomere medicine.disease Blotting Southern Leukemia Nucleoproteins Oncology Cancer research Female Carcinogenesis |
| Zdroj: | Clinical Cancer Research. 11:5347-5355 |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | Purpose: Telomeres are specialized nucleoprotein complexes that protect and confer stability upon chromosome ends. Loss of telomere function as a consequence of proliferation-associated sequence attrition results in genome instability, which may facilitate carcinogenesis by generating growth-promoting mutations. However, unlimited cellular proliferation requires the maintenance of telomeric DNA; thus, the majority of tumor cells maintain their telomeres either through the activity of telomerase or via a mechanism known as alternative lengthening of telomeres (ALT). Recent data suggest that constitutive telomere maintenance may not be required in all tumor types. Here we assess the role and requirement of telomere maintenance in liposarcoma.Experimental Design: Tumor samples were analyzed with respect to telomerase activity, telomere length, and the presence of ALT-specific subcellular structures, ALT-associated promyelocytic leukemia nuclear bodies. This multiassay assessment improved the accuracy of categorization.Results: Our data reveal a significant incidence (24%) of ALT-positive liposarcomas, whereas telomerase is used at a similar frequency (27%). A large number of tumors (49%) do not show characteristics of telomerase or ALT. In addition, telomere length was always shorter in recurrent disease, regardless of the telomere maintenance mechanism.Conclusions: These results suggest that approximately one half of liposarcomas either employ a novel constitutively active telomere maintenance mechanism or lack such a mechanism. Analysis of recurrent tumors suggests that liposarcomas can develop despite limiting or undetectable activity of a constitutively active telomere maintenance mechanism. |
| Databáze: | OpenAIRE |
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