HTERT gene amplification and increased mRNA expression in central nervous system embryonal tumors
HTERT gene amplification and increased mRNA expression in central nervous system embryonal tumors
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DOI：
10.1016/s0002-9440(10)64311-8
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发表时间：
2003-06-01
影响因子：
6
通讯作者：
Eberhart, CG
中科院分区：
文献类型：
--
作者：
Fan, X;Wang, YY;Eberhart, CG
5P15是一个染色体区域，包括人类端粒酶催化蛋白亚基（bTERT）基因，在几个髓母细胞瘤中有高水平的增加。因此，我们使用差异PCR分析了一组髓母细胞瘤和其他胚胎性脑肿瘤的hTERT基因剂量。36例肿瘤中有15例（42%）检测到hTERT位点扩增。为了将基因扩增与信息水平联系起来，我们采用实时定量PCR检测了50例胚胎性脑肿瘤中hTERT mRNA的表达。除1例外，所有病例均检测到hTERT mRNA， mRNA水平与基因剂量显著相关（r = 0.82）。生存数据的Log-rank分析显示，hTERT mRNA水平高的成神经管细胞瘤患者有临床预后较差的趋势，但临床随访时间较短，相关性无统计学意义（P = 0.078）。采用比较基因组杂交法进一步分析bTERT基因剂量和mRNA水平最高的复发性髓质上皮瘤。bTERT在复发肿瘤中扩增，但在原发病变中未扩增，提示该位点可能参与肿瘤进展。我们的数据表明，bTERT基因扩增在胚胎性脑肿瘤中相对常见，并且hTERT MRNA表达的增加可能与肿瘤的生物学侵袭性行为有关。
High-level gains at 5P15, a chromosomal region including the human telomerase catalytic protein subunit (bTERT) gene, have been documented in several medulloblastomas. We therefore analyzed hTERT gene dosage in a group of medulloblastomas and other embryonal brain tumors using differential PCR. Amplification of the hTERT locus was detected in 15 of 36 (42%) tumors examined. To correlate gene amplification with message level, we used real-time quantitative PCR to measure hTERT mRNA in 50 embryonal brain tumors. hTERT mRNA was detected in all but one of these cases, and mRNA level correlated significantly with gene dosage (r = 0.82). Log-rank analysis of survival data revealed a trend toward poor clinical outcomes in patients with medulloblastomas containing high hTERT mRNA levels, but clinical follow-up was relatively short and the association was not statistically significant (P = 0.078). Comparative genomic hybridization was used to further analyze the tumor with the greatest bTERT gene dosage and mRNA level, a recurrent medulloepithelioma. bTERT was amplified in the recurrent tumor but not in the primary lesion, suggesting this locus can be involved in tumor progression. Our data indicate that bTERT gene amplification is relatively common in embryonal brain tumors, and that increased expression of hTERT MRNA may be associated with biologically aggressive tumor behavior.