This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Costa, A. Articles by Zaffaroni, N. Search for Related Content PubMed PubMed Citation Articles by Costa, A. Articles by Zaffaroni, N.

Telomere Maintenance Mechanisms in Liposarcomas: Association with Histologic Subtypes and Disease Progression

Departments of ¹ Experimental Oncology and Laboratories, ² Pathology, ³ Biostatistics, and ⁴ Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy and ⁵ Children's Medical Research Institute, Westmead, Sydney, Australia

Requests for reprints: Nadia Zaffaroni, Unit #10, Department of Experimental Oncology and Laboratories, Istituto Nazionale Tumori, via Venezian 1, 20133 Milano, Italy. Phone: 39-02-2390-3260; Fax: 39-02-2390-3052; E-mail: nadia.zaffaroni{at}istitutotumori.mi.it.

Human cancer cells maintain telomeres by telomerase activity (TA) or by alternative lengthening of telomeres (ALT). We proposed to define the prevalence of the two telomere maintenance mechanisms (TMM), to assess their association with histology, and to compare their prognostic relevance in a series of 93 patients with liposarcoma. ALT was detected by assaying ALT-associated promyelocytic leukemia nuclear bodies and TA was assayed using the telomeric repeat amplification protocol. ALT or TA was found in 25.9% or 26.6% of 139 tested liposarcoma lesions, respectively. Three lesions were ALT+/TA+ whereas 50% of lesions did not show any known TMM. TMM phenotype was consistent during disease progression. ALT was prevalent in dedifferentiated and in grade 3 liposarcomas whereas TA prevailed in most round-cell myxoid and in grade 2 liposarcomas. ALT and TA incidence was similar in primary and recurrent lesions whereas metastases were more frequently TA+ than ALT+ (59% versus 18%; P = 0.04). TMM presence negatively affected patient prognosis (P = 0.001): increased mortality was associated with positivity for TA (P = 0.038) or ALT (P < 0.0001) compared with TMM absence. ALT proved to be a stronger prognostic discriminant of increased mortality than TA even when adjusted for tumor location, grade, and histology (hazard ratio for cause-specific death, 3.58 versus 1.15). Our results indicate that ALT can support fully malignant liposarcomas and is associated with unfavorable disease outcome. (Cancer Res 2006; 66(17): 8918-24)

This article has been cited by other articles:

				T. Else Telomeres and telomerase in adrenocortical tissue maintenance, carcinogenesis, and aging J. Mol. Endocrinol., October 1, 2009; 43(4): 131 - 141. [Abstract] [Full Text] [PDF]

				T. MATSUO, S. SHIMOSE, T. KUBO, J. FUJIMORI, Y. YASUNAGA, and M. OCHI Telomeres and Telomerase in Sarcomas Anticancer Res, October 1, 2009; 29(10): 3833 - 3836. [Abstract] [Full Text] [PDF]

				R. Villa, M. G. Daidone, R. Motta, L. Venturini, C. De Marco, A. Vannelli, S. Kusamura, D. Baratti, M. Deraco, A. Costa, et al. Multiple Mechanisms of Telomere Maintenance Exist and Differentially Affect Clinical Outcome in Diffuse Malignant Peritoneal Mesothelioma Clin. Cancer Res., July 1, 2008; 14(13): 4134 - 4140. [Abstract] [Full Text] [PDF]

				T. Else, T. J. Giordano, and G. D. Hammer Evaluation of Telomere Length Maintenance Mechanisms in Adrenocortical Carcinoma J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1442 - 1449. [Abstract] [Full Text] [PDF]

				J. E. Johnson, E. J. Gettings, J. Schwalm, J. Pei, J. R. Testa, S. Litwin, M. von Mehren, and D. Broccoli Whole-Genome Profiling in Liposarcomas Reveals Genetic Alterations Common to Specific Telomere Maintenance Mechanisms Cancer Res., October 1, 2007; 67(19): 9221 - 9228. [Abstract] [Full Text] [PDF]

				S. A. Compton, J.-H. Choi, A. J. Cesare, S. Ozgur, and J. D. Griffith Xrcc3 and Nbs1 Are Required for the Production of Extrachromosomal Telomeric Circles in Human Alternative Lengthening of Telomere Cells Cancer Res., February 15, 2007; 67(4): 1513 - 1519. [Abstract] [Full Text] [PDF]