Divergent patterns of telomere maintenance mechanisms among human sarcomas: Sharply contrasting prevalence of the alternative lengthening of telomeres mechanism in Ewing's sarcomas and osteosarcomas
Divergent patterns of telomere maintenance mechanisms among human sarcomas: Sharply contrasting prevalence of the alternative lengthening of telomeres mechanism in Ewing's sarcomas and osteosarcomas
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DOI：
10.1002/gcc.20074
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发表时间：
2004-10-01
影响因子：
3.7
通讯作者：
Ladanyi, M
中科院分区：
文献类型：
--
作者：
Ulaner, GA;Hoffman, AR;Ladanyi, M
人类肿瘤中有两种类型的端粒维持机制：端粒酶激活和端粒交替延长(ALT)。尽管绝大多数上皮性肿瘤依赖于端粒酶的激活，许多间叶性肿瘤依赖ALT维持端粒，但在这一肿瘤组中，移位相关肉瘤使用的TMM尚未得到系统研究。我们研究了30个未培养的肿瘤样本和10个尤文氏肉瘤细胞系的端粒长度和端粒酶的表达和活性，尤文氏肉瘤是一种典型的移位相关肉瘤，我们将这些数据与对60例骨肉瘤的相同分析进行了比较，骨肉瘤是最常见的缺乏特异性移位的肉瘤类型。端粒酶活性在21例尤文肉瘤标本(70%)和9例尤文肉瘤细胞株中表达。ALT的证据，表明存在长的和不同种类的端粒，只在没有端粒酶活性的细胞系中观察到，在30例尤文氏肉瘤样本中没有观察到。9例肿瘤缺乏端粒酶活性的尤文肉瘤患者在年龄、分期、EWSR1-FLI1融合类型、TP53点突变发生率和总生存期方面与其余患者没有显著差异。尤文肉瘤中ALT的低患病率与我们在60例骨肉瘤TMM上的数据形成了鲜明对比，60例骨肉瘤中有38例ALT(P<；0.0001)。目前的研究结合其他肉瘤类型的最新发表的数据表明，在没有ALT的情况下，端粒酶激活的优势可能是具有特定染色体易位的肉瘤的特征(如尤文氏肉瘤)，而ALT的高患病率似乎是具有非特异性复杂核型的肉瘤的典型特征(如骨肉瘤)。(C)2004年Wiley-Liss公司
Two types of telomere maintenance mechanisms (TMMs) have been described in human tumors: telomerase activation and alternative lengthening of telomeres (ALT). Although the vast majority of epithelial tumors rely on telomerase activation, many mesenchymal tumors rely on ALT for telomere maintenance, but within this tumor group, the TMMs used by translocation-associated sarcomas have not been systematically studied. We studied telomere lengths and telomerase expression and activity in 30 uncultured tumor samples and in 10 cell lines of Ewing's sarcoma, a prototypical translocation-associated sarcoma, and compared the data to an identical analysis of 60 osteosarcomas, the most common type of sarcoma lacking a specific translocation. Telomerase activity was demonstrated in 21 Ewing's sarcoma tumor samples (70%) and in 9 of 10 Ewing's sarcoma cell lines. Evidence of ALT, indicated by the presence of long and heterogeneous telomeres, was observed only in the cell line without telomerase activity and in none of the 30 Ewing's sarcoma tumor samples. The 9 Ewing's sarcoma patients whose tumors lacked detectable telomerase activity did not differ significantly from the remaining patients in age, stage, EWSR1-FLI1 fusion type, prevalence of TP53 point mutations, or overall survival. The low prevalence of ALT in Ewing's sarcoma contrasted sharply with our data on TMMs in 60 osteosarcomas, which showed ALT in 38 of 60 cases (P < 0.0001). The present study, together with emerging published data on other sarcoma types, suggests that a predominance of telomerase activation in the absence of ALT may characterize sarcomas with specific chromosomal translocations (such as Ewing's sarcoma), whereas a high prevalence of ALT appears typical of sarcomas with nonspecific complex karyotypes (such as osteosarcoma). (C) 2004 Wiley-Liss, Inc.