|Title:||Alternative lengthening of telomeres phenotype in malignant vascular tumors is highly associated with loss of ATRX expression and is frequently observed in hepatic angiosarcomas||Authors:||JAU-YU LIAU
|Issue Date:||2015||Publisher:||W.B. Saunders||Journal Volume:||46||Journal Issue:||9||Start page/Pages:||1360-1366||Source:||Human Pathology||Abstract:||
Summary Alternative lengthening of telomeres (ALT) is a mechanism using homologous recombination to maintain telomere length and sustain limitless replicability of cancer cells. Recently, ALT has been found to be associated with inactivation of either α-thalassemia/mental retardation syndrome X-linked (ATRX) or death domain-associated (DAXX) protein. In this study, 119 tumors (88 angiosarcomas, 11 epithelioid hemangioendotheliomas, and 20 Kaposi sarcomas) were analyzed to determine the ALT status, its relationship to loss of ATRX/DAXX expression, and the clinicopathological features. In addition, the mutation status in the telomerase reverse transcriptase gene (TERT) promoter was also studied. Loss of ATRX expression was observed in 21% (16/77) of the primary angiosarcomas and 9% (1/11) of epithelioid hemangioendotheliomas. DAXX expression was intact in all but 2 ATRX-deficient angiosarcomas. Telomere-specific fluorescence in situ hybridization assay showed 28% (17/61) of the primary angiosarcomas were ALT positive. Remarkably, ALT was highly associated with loss of ATRX expression: all but 2 ALT-positive angiosarcomas were ATRX deficient. Notably, hepatic angiosarcomas were frequently ATRX deficient (8/13) and/or ALT positive (8/12). None of the secondary angiosarcomas were ATRX/DAXX deficient or ALT positive. The only ATRX-deficient epithelioid hemangioendothelioma was positive for ALT. Forty-seven angiosarcomas were tested for TERT promoter mutation. Despite the fact that angiosarcoma occurs most commonly in sun-damaged skin, mutation was detected in only 1 radiation-associated angiosarcoma (2%). We conclude that ALT is an important telomere maintenance mechanism in primary angiosarcomas. This feature is highly associated with loss of ATRX expression and is frequently observed in hepatic angiosarcomas. ? 2015 Elsevier Inc.
|ISSN:||0046-8177||DOI:||10.1016/j.humpath.2015.05.019||SDG/Keyword:||alpha thalassemia mental retardation syndrome X linked protein; death domain associated protein; protein; telomerase reverse transcriptase; unclassified drug; ATRX protein, human; DNA helicase; nuclear protein; telomerase; TERT protein, human; tumor marker; adult; aged; Article; breast cancer; clinical feature; cystosarcoma phylloides; female; fluorescence in situ hybridization; follow up; gene mutation; hemangioendothelioma; hepatic angiosarcoma; histopathology; human; human tissue; Kaposi sarcoma; liver sarcoma; major clinical study; male; malignant peripheral nerve sheath tumor; mitosis rate; nasopharynx carcinoma; phenotype; promoter region; protein expression; survival; telomere homeostasis; undifferentiated carcinoma; uterine cervix carcinoma; vascular tumor; angiosarcoma; down regulation; enzymology; genetics; immunohistochemistry; liver tumor; middle aged; mortality; mutation; nucleotide sequence; pathology; prognosis; skin tumor; telomere; Adult; Aged; DNA Helicases; DNA Mutational Analysis; Down-Regulation; Female; Hemangioendothelioma, Epithelioid; Hemangiosarcoma; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Liver Neoplasms; Male; Middle Aged; Mutation; Nuclear Proteins; Prognosis; Promoter Regions, Genetic; Sarcoma, Kaposi; Skin Neoplasms; Telomerase; Telomere; Telomere Homeostasis; Tumor Markers, Biological
|Appears in Collections:||病理學科所|
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