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  1. NTU Scholars
  2. 醫學院
  3. 病理學科所
Please use this identifier to cite or link to this item: https://scholars.lib.ntu.edu.tw/handle/123456789/473699
Title: Alternative lengthening of telomeres and loss of ATRX are frequent events in pleomorphic and dedifferentiated liposarcomas
Authors: JEN-CHIEH LEE 
YUNG-MING JENG 
JAU-YU LIAU 
JIA-HUEI TSAI 
Hsu H.-H.
CHING-YAO YANG 
Issue Date: 2015
Publisher: Nature Publishing Group
Journal Volume: 28
Journal Issue: 8
Start page/Pages: 1064-1073
Source: Modern Pathology
Abstract: 
Telomerase activation and alternative lengthening of telomeres are two major mechanisms of telomere length maintenance. Soft tissue sarcomas appear to use the alternative lengthening of telomeres more frequently. Loss of α-thalassemia/mental retardation syndrome X-linked (ATRX) or death domain-associated protein 6 (DAXX) expression has been implicated in the pathogenesis of alternative telomere lengthening in pancreatic endocrine neoplasm and glioma. The mechanism leading to the alternative lengthening of telomeres in liposarcoma remains unknown. Whereas alternative telomere lengthening was determined to be an indicator of poor prognosis in liposarcomas as a whole, its prognostic power has not been verified in any subtype of liposarcoma. In this study, we characterized the status of alternative telomere lengthening and expression of ATRX and DAXX in 111 liposarcomas (28 well-differentiated, 52 dedifferentiated, 20 myxoid or round cell, and 11 pleomorphic liposarcomas) by telomere fluorescence in situ hybridization and immunohistochemistry, respectively. Alternative lengthening of telomere was observed in 0% (0/16) of well-differentiated, 30% (14/46) of dedifferentiated, 5% (1/19) of myxoid or round cell, and 80% (8/10) of pleomorphic liposarcomas. Eighteen (16%) and one (1%) tumors were negative for ATRX and DAXX immunostaining, respectively. Remarkably, all cases with loss of either ATRX or DAXX expression had alternative lengthening of telomeres, and 83% (19/23) of tumors that had alternative lengthening of telomeres showed loss of either protein. The correlation between loss of either ATRX or DAXX and alternative telomere lengthening was 100% in dedifferentiated liposarcoma. The presence of alternative telomere lengthening in dedifferentiated liposarcoma suggested poor overall survival (hazard ratio=1.954, P=0.077) and was the most significant indicator of short progression-free survival (hazard ratio=3.119, P=0.003). In conclusion, we found that ATRX loss was the most likely mechanism of alternative telomere lengthening in liposarcoma and alternative telomere lengthening was a prognostic factor of poor outcome in dedifferentiated liposarcoma. ? 2015 USCAP, Inc All rights reserved.
URI: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84938418620&doi=10.1038%2fmodpathol.2015.67&partnerID=40&md5=93659278cc3e21db414325a2bc936386
https://scholars.lib.ntu.edu.tw/handle/123456789/473699
ISSN: 0893-3952
DOI: 10.1038/modpathol.2015.67
SDG/Keyword: adult; aged; alpha thalassemia mental retardation syndrome X linked gene; Article; death domain associated protein 6 gene; dedifferentiated liposarcoma; female; fluorescence in situ hybridization; gene; gene expression; human; human tissue; immunohistochemistry; liposarcoma; major clinical study; male; myxosarcoma; overall survival; phenotype; pleomorphic liposarcoma; priority journal; progression free survival; protein depletion; telomere homeostasis; well differentiated liposarcoma; cell dedifferentiation; disease course; disease free survival; down regulation; enzymology; genetics; Kaplan Meier method; liposarcoma; middle aged; mortality; pathology; proportional hazards model; risk factor; time factor; treatment outcome; very elderly; ATRX protein, human; DAXX protein, human; DNA helicase; nuclear protein; signal transducing adaptor protein; tumor marker; Adaptor Proteins, Signal Transducing; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cell Dedifferentiation; Disease Progression; Disease-Free Survival; DNA Helicases; Down-Regulation; Female; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Kaplan-Meier Estimate; Liposarcoma; Male; Middle Aged; Nuclear Proteins; Proportional Hazards Models; Risk Factors; Telomere Homeostasis; Time Factors; Treatment Outcome
[SDGs]SDG3
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臺大位居世界頂尖大學之列,為永久珍藏及向國際展現本校豐碩的研究成果及學術能量,圖書館整合機構典藏(NTUR)與學術庫(AH)不同功能平台,成為臺大學術典藏NTU scholars。期能整合研究能量、促進交流合作、保存學術產出、推廣研究成果。

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