High level of telomerase RNA gene expression is associated with chromatin modification, the ALT phenotype and poor prognosis in liposarcoma.
High level of telomerase RNA gene expression is associated with chromatin modification, the ALT phenotype and poor prognosis in liposarcoma.
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DOI：
10.1038/sj.bjc.6604328
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发表时间：
2008-04-22
影响因子：
8.8
通讯作者：
Keith WN
中科院分区：
文献类型：
--
作者：
Cairney CJ;Hoare SF;Daidone MG;Zaffaroni N;Keith WN
端粒长度的维持有两种已知的机制，端粒酶的激活或端粒的交替延长（ALT）。ALT途径在间充质来源的肿瘤中更常见地被激活，尽管参与细胞激活端粒酶或ALT的决定的机制目前尚不清楚，并且不存在分子标记物来定义ALT表型。我们先前已经在细胞系模型中显示了染色质重塑、端粒酶基因表达和ALT之间的关联。在此，我们评估这些发现并研究其在一组脂肪肉瘤组织样本中的预后意义，以了解ALT表型的生物学基础。脂肪肉瘤样本分为三组：端粒酶阳性（Tel+）; ALT阳性; ALT-/Tel-。与ALT-/Tel-样本相比，ALT和Tel+样本中hTR表达增加，而Tel+样本中hTERT表达增加，这两组之间端粒酶基因表达的差异很明显。一小组染色质修饰的研究显示，与hTR表达相关的乙酰基H3的结合显著增加。我们证实ALT表型的存在与不良预后相关，此外，我们首次发现hTR表达与脂肪肉瘤患者不良预后直接相关。
Telomere length is maintained by two known mechanisms, activation of telomerase or alternative lengthening of telomeres (ALT). The ALT pathway is more commonly activated in tumours of mesenchymal origin, although the mechanisms involved in the decision of a cell to activate either telomerase or ALT are unknown at present and no molecular markers exist to define the ALT phenotype. We have previously shown an association between chromatin remodelling, telomerase gene expression and ALT in cell line models. Here, we evaluate these findings and investigate their prognostic significance in a panel of liposarcoma tissue samples to understand the biology underlying the ALT phenotype. Liposarcoma samples were split into three groups: telomerase positive (Tel+); ALT positive; ALT−/Tel−. Differences in telomerase gene expression were evident between the groups with increased expression of hTR in ALT and Tel+ compared to ALT−/Tel− samples and increased hTERT in Tel+ samples only. Investigation of a small panel of chromatin modifications revealed significantly increased binding of acetyl H3 in association with hTR expression. We confirm that the presence of the ALT phenotype is associated with poor prognosis and in addition, for the first time, we show a direct association between hTR expression and poor prognosis in liposarcoma patients.
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影响因子：
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作者：
Anderson, CJ;Hoare, SF;Keith, WN
通讯作者：
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