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Prevalence of the alternative lengthening of telomeres telomere maintenance mechanism in human cancer subtypes

Heaphy, Christopher M. and Subhawong, Andrea P. and Hong, Seung-Mo and Goggins, Michael G. and Montgomery, Elizabeth A. and Gabrielson, Edward and Netto, George J. and Epstein, Jonathan I. and Lotan, Tamara L. and Westra, William H. and Shih, Ie-Ming and Iacobuzio-Donahue, Christine A. and Maitra, Anirban and Li, Qing K. and Eberhart, Charles G. and Taube, Janis M. and Rakheja, Dinesh and Kurman, Robert J. and Wu, T. C. and Roden, Richard B. and Argani, Pedram and De Marzo, Angelo M. and Terracciano, Luigi and Torbenson, Michael and Meeker, Alan K.. (2011) Prevalence of the alternative lengthening of telomeres telomere maintenance mechanism in human cancer subtypes. American journal of pathology, Vol. 179, no. 4. pp. 1608-1615.

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Official URL: http://edoc.unibas.ch/dok/A6006967

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Abstract

Approximately 10% to 15% of human cancers lack detectable telomerase activity, and a subset of these maintain telomere lengths by the telomerase-independent telomere maintenance mechanism termed alternative lengthening of telomeres (ALT). The ALT phenotype, relatively common in subtypes of sarcomas and astrocytomas, has rarely been reported in epithelial malignancies. However, the prevalence of ALT has not been thoroughly assessed across all cancer types. We therefore comprehensively surveyed the ALT phenotype in a broad range of human cancers. In total, two independent sets comprising 6110 primary tumors from 94 different cancer subtypes, 541 benign neoplasms, and 264 normal tissue samples were assessed by combined telomere-specific fluorescence in situ hybridization and immunofluorescence labeling for PML protein. Overall, ALT was observed in 3.73% (228/6110) of all tumor specimens, but was not observed in benign neoplasms or normal tissues. This is the first report of ALT in carcinomas arising from the bladder, cervix, endometrium, esophagus, gallbladder, kidney, liver, and lung. Additionally, this is the first report of ALT in medulloblastomas, oligodendrogliomas, meningiomas, schwannomas, and pediatric glioblastoma multiformes. Previous studies have shown associations between ALT status and prognosis in some tumor types; thus, further studies are warranted to assess the potential prognostic significance and unique biology of ALT-positive tumors. These findings may have therapeutic consequences, because ALT-positive cancers are predicted to be resistant to anti-telomerase therapies.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Molekulare Pathologie (Terracciano)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Molekulare Pathologie (Terracciano)
UniBasel Contributors:Terracciano, Luigi M.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society for Investigative Pathology
ISSN:0002-9440
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:27 Feb 2014 15:46
Deposited On:27 Feb 2014 15:46

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