Jay E Johnson1, Dominique Broccoli. 1. Department of Laboratory Oncology Research, Curtis and Elizabeth Anderson Cancer Institute, Memorial Health University Medical Center, Savannah, Georgia 31404, USA.
Abstract
PURPOSE OF REVIEW: To examine the activation of telomere maintenance in a variety of sarcoma subtypes, and to review the consequences of telomere maintenance with respect to genome stability and tumor progression. RECENT FINDINGS: A hallmark of tumor cells is replicative immortality, which can be achieved, in part, by the activation of a telomere maintenance mechanism. A significant proportion of tumors show activation of telomerase, a specialized enzyme that adds telomeric repeats to pre-existing telomeres. Recent work has demonstrated, however, that a telomerase-independent mechanism called ALT (alternative lengthening of telomeres) is activated as frequently as telomerase in a variety of tumor types, particularly those of mesenchymal origin. Accordingly, panels of mesenchymal tumors have been interrogated for telomere maintenance mechanism, as well as characteristics such as tumor grade and patient survival. SUMMARY: These studies indicate a strong positive correlation between the activation of a telomere maintenance mechanism and tumor progression in sarcomas. In addition, the activation of either ALT or telomerase is correlated with poorer patient prognosis as compared with a lack of telomere maintenance. Ongoing studies aimed at elucidating the roles of ALT and telomerase in tumorigenesis should ultimately allow for the development of strategies to improve treatment of these malignancies.
PURPOSE OF REVIEW: To examine the activation of telomere maintenance in a variety of sarcoma subtypes, and to review the consequences of telomere maintenance with respect to genome stability and tumor progression. RECENT FINDINGS: A hallmark of tumor cells is replicative immortality, which can be achieved, in part, by the activation of a telomere maintenance mechanism. A significant proportion of tumors show activation of telomerase, a specialized enzyme that adds telomeric repeats to pre-existing telomeres. Recent work has demonstrated, however, that a telomerase-independent mechanism called ALT (alternative lengthening of telomeres) is activated as frequently as telomerase in a variety of tumor types, particularly those of mesenchymal origin. Accordingly, panels of mesenchymal tumors have been interrogated for telomere maintenance mechanism, as well as characteristics such as tumor grade and patient survival. SUMMARY: These studies indicate a strong positive correlation between the activation of a telomere maintenance mechanism and tumor progression in sarcomas. In addition, the activation of either ALT or telomerase is correlated with poorer patient prognosis as compared with a lack of telomere maintenance. Ongoing studies aimed at elucidating the roles of ALT and telomerase in tumorigenesis should ultimately allow for the development of strategies to improve treatment of these malignancies.
Authors: Thibaud Jegou; Inn Chung; Gerrit Heuvelman; Malte Wachsmuth; Sabine M Görisch; Karin M Greulich-Bode; Petra Boukamp; Peter Lichter; Karsten Rippe Journal: Mol Biol Cell Date: 2009-02-11 Impact factor: 4.138
Authors: Anne Sofie Brems-Eskildsen; Karsten Zieger; Helle Toldbod; Cherie Holcomb; Russell Higuchi; Francisco Mansilla; Pia P Munksgaard; Michael Borre; Torben F Ørntoft; Lars Dyrskjøt Journal: BMC Cancer Date: 2010-11-24 Impact factor: 4.430