Telomere Maintenance Mechanisms in Cancer.
Telomere Maintenance Mechanisms in Cancer.
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DOI：
10.3390/genes9050241
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发表时间：
2018-05-03
期刊：
影响因子：
3.5
通讯作者：
Vinagre J
中科院分区：
文献类型：
--
作者：
Gaspar TB;Sá A;Lopes JM;Sobrinho-Simões M;Soares P;Vinagre J
肿瘤细胞可以采用端粒维持机制(TMM)来避免端粒缩短，端粒缩短是细胞连续分裂的必然过程。在大多数肿瘤细胞中，端粒长度(TL)通过端粒酶的重新激活来维持，而一小部分通过端粒酶非依赖的端粒交替延长(ALT)机制获得不朽。在过去的几年里，产生了大量的数据，并对不同的TMM进行了详细的报告和解释，这得益于具有重大意义的基因组规模研究。在这篇综述中，我们讨论了肿瘤细胞中的七种不同的TMM：TERT启动子的突变(TERTp)、TERT和TERC基因的扩增、TERT基因及其启动子的多态变异、TERT基因的重排、表观遗传学变化、ALT和未定义的TMM(NDTMM)。我们收集了过去几年中288篇论文中报道的5万多名患者的信息。这种广泛的数据收集使我们能够按器官/系统和组织类型描绘人类肿瘤中TERTp突变、TERT和TERC扩增以及ALT的流行情况。基于这些信息，我们讨论了上述机制在不同设置下对恶性转化过程可能产生的未来临床影响，并为筛查、预后和患者管理分层提供了见解。
Tumour cells can adopt telomere maintenance mechanisms (TMMs) to avoid telomere shortening, an inevitable process due to successive cell divisions. In most tumour cells, telomere length (TL) is maintained by reactivation of telomerase, while a small part acquires immortality through the telomerase-independent alternative lengthening of telomeres (ALT) mechanism. In the last years, a great amount of data was generated, and different TMMs were reported and explained in detail, benefiting from genome-scale studies of major importance. In this review, we address seven different TMMs in tumour cells: mutations of the TERT promoter (TERTp), amplification of the genes TERT and TERC, polymorphic variants of the TERT gene and of its promoter, rearrangements of the TERT gene, epigenetic changes, ALT, and non-defined TMM (NDTMM). We gathered information from over fifty thousand patients reported in 288 papers in the last years. This wide data collection enabled us to portray, by organ/system and histotypes, the prevalence of TERTp mutations, TERT and TERC amplifications, and ALT in human tumours. Based on this information, we discuss the putative future clinical impact of the aforementioned mechanisms on the malignant transformation process in different setups, and provide insights for screening, prognosis, and patient management stratification.
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影响因子：
30.8
作者：
Barthel FP;Wei W;Tang M;Martinez-Ledesma E;Hu X;Amin SB;Akdemir KC;Seth S;Song X;Wang Q;Lichtenberg T;Hu J;Zhang J;Zheng S;Verhaak RG
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Verhaak RG
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Karlseder J
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network. Electronic address: wheeler@bcm.edu;Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
16.6
作者：
Arora, Rajika;Lee, Yongwoo;Wischnewski, Harry;Brun, Catherine M.;Schwarz, Tobias;Azzalin, Claus M.
通讯作者：
Azzalin, Claus M.
影响因子：
2.6
作者：
Bechter, OE;Eisterer, W;Thaler, J
通讯作者：
Thaler, J