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端粒酶逆转录酶（hTERT）和端粒替代延长（ALT）小儿脑肿瘤中预复制复合体基因表达的变化。

Changes in the Expression of Pre-Replicative Complex Genes in hTERT and ALT Pediatric Brain Tumors.

作者信息

Idilli Aurora Irene, Pagani Francesca, Kerschbamer Emanuela, Berardinelli Francesco, Bernabé Manuel, Cayuela María Luisa, Piazza Silvano, Poliani Pietro Luigi, Cusanelli Emilio, Mione Maria Caterina

机构信息

Department of Cellular, Computational and Integrative Biology-CIBIO, University of Trento, Via Sommarive 9, 38123 Trento, Italy.

Pathology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.

出版信息

Cancers (Basel). 2020 Apr 22;12(4):1028. doi: 10.3390/cancers12041028.

DOI:10.3390/cancers12041028
PMID:32331249
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7226177/
Abstract

: The up-regulation of a telomere maintenance mechanism (TMM) is a common feature of cancer cells and a hallmark of cancer. Routine methods for detecting TMMs in tumor samples are still missing, whereas telomerase targeting treatments are becoming available. In paediatric cancers, alternative lengthening of telomeres (ALT) is found in a subset of sarcomas and malignant brain tumors. ALT is a non-canonical mechanism of telomere maintenance developed by cancer cells with no-functional telomerase. : To identify drivers and/or markers of ALT, we performed a differential gene expression analysis between two zebrafish models of juvenile brain tumors, that differ only for the telomere maintenance mechanism adopted by tumor cells: one is ALT while the other is telomerase-dependent. : Comparative analysis of gene expression identified five genes of the pre-replicative complex, , and as upregulated in ALT. We searched for a correlation between telomerase levels and expression of the pre-replicative complex genes in a cohort of paediatric brain cancers and identified a counter-correlation between telomerase expression and the genes of the pre-replicative complex. Moreover, the analysis of ALT markers in a group of 20 patients confirmed the association between ALT and increased RPA and decreased H3K9 localization at telomeres. : Our study suggests that telomere maintenance mechanisms may act as a driver of telomeric DNA replication and chromatin status in brain cancers and identifies markers of ALT that could be exploited for precise prognostic and therapeutic purposes.

摘要

端粒维持机制（TMM）的上调是癌细胞的一个常见特征，也是癌症的一个标志。目前仍缺乏在肿瘤样本中检测TMM的常规方法，而靶向端粒酶的治疗方法正在出现。在儿童癌症中，端粒的替代延长（ALT）在一部分肉瘤和恶性脑肿瘤中被发现。ALT是癌细胞发展出的一种非经典端粒维持机制，这些癌细胞的端粒酶无功能。

为了鉴定ALT的驱动因素和/或标志物，我们在两种幼年脑肿瘤斑马鱼模型之间进行了差异基因表达分析，这两种模型仅在肿瘤细胞采用的端粒维持机制上有所不同：一种是ALT，另一种是端粒酶依赖性的。

基因表达的比较分析确定了预复制复合体的五个基因，即 、 、 、 和 ，在ALT中上调。我们在一组儿童脑癌中寻找端粒酶水平与预复制复合体基因表达之间的相关性，并确定了端粒酶表达与预复制复合体基因之间的负相关。此外，对一组20名患者的ALT标志物分析证实了ALT与端粒处RPA增加和H3K9定位减少之间的关联。

我们的研究表明，端粒维持机制可能是脑癌中端粒DNA复制和染色质状态的驱动因素，并鉴定出了可用于精确预后和治疗目的的ALT标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bcd/7226177/382b3cc1c1aa/cancers-12-01028-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bcd/7226177/a09fff32609e/cancers-12-01028-g001a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bcd/7226177/6f8fbf192fe8/cancers-12-01028-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bcd/7226177/b1ac16212762/cancers-12-01028-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bcd/7226177/bb7861bac1cd/cancers-12-01028-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bcd/7226177/382b3cc1c1aa/cancers-12-01028-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bcd/7226177/a09fff32609e/cancers-12-01028-g001a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bcd/7226177/6f8fbf192fe8/cancers-12-01028-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bcd/7226177/b1ac16212762/cancers-12-01028-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bcd/7226177/bb7861bac1cd/cancers-12-01028-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bcd/7226177/382b3cc1c1aa/cancers-12-01028-g005.jpg

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2
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