Systematic analysis of telomere length and somatic alterations in 31 cancer types

被引:483
作者
Barthel, Floris P. [1 ,2 ,3 ]
Wei, Wei [4 ]
Tang, Ming [3 ]
Martinez-Ledesma, Emmanuel [3 ,5 ]
Hu, Xin [3 ,6 ]
Amin, Samirkumar B. [3 ,7 ]
Akdemir, Kadir C. [3 ]
Seth, Sahil [8 ]
Song, Xingzhi [8 ]
Wang, Qianghu [3 ,9 ]
Lichtenberg, Tara [10 ]
Hu, Jian [11 ]
Zhang, Jianhua [8 ]
Zheng, Siyuan [3 ,5 ]
Verhaak, Roel G. W. [1 ,3 ,9 ]
机构
[1] Jackson Lab Genom Med, Farmington, CT 06032 USA
[2] Vrije Univ Amsterdam, Med Ctr, Oncol Grad Sch Amsterdam, Amsterdam, Netherlands
[3] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA
[4] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA
[5] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA
[6] Univ Texas Grad Sch Biomed Sci Houston, Program Biostat Bioinformat & Syst Biol, Houston, TX USA
[7] Baylor Coll Med, Grad Program Struct & Computat Biol & Mol Biophys, Houston, TX 77030 USA
[8] Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Houston, TX 77030 USA
[9] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA
[10] Nationwide Childrens Hosp, Biopathol Ctr, Columbus, OH USA
[11] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA
基金
美国国家卫生研究院;
关键词
TERT PROMOTER MUTATIONS; RENAL-CELL CARCINOMA; REVERSE-TRANSCRIPTASE; CATALYTIC SUBUNIT; GENE-EXPRESSION; HUMAN TUMORS; RNA; METHYLATION; LANDSCAPE; CHROMATIN;
D O I
10.1038/ng.3781
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Cancer cells survive cellular crisis through telomere maintenance mechanisms. We report telomere lengths in 18,430 samples, including tumors and non-neoplastic samples, across 31 cancer types. Telomeres were shorter in tumors than in normal tissues and longer in sarcomas and gliomas than in other cancers. Among 6,835 cancers, 73% expressed telomerase reverse transcriptase (TERT), which was associated with TERT point mutations, rearrangements, DNA amplifications and transcript fusions and predictive of telomerase activity. TERT promoter methylation provided an additional deregulatory TERT expression mechanism. Five percent of cases, characterized by undetectable TERT expression and alterations in ATRX or DAXX, demonstrated elongated telomeres and increased telomeric repeat-containing RNA (TERRA). The remaining 22% of tumors neither expressed TERT nor harbored alterations in ATRX or DAXX. In this group, telomere length positively correlated with TP53 and RB1 mutations. Our analysis integrates TERT abnormalities, telomerase activity and genomic alterations with telomere length in cancer.
引用
收藏
页码:349 / 357
页数:9
相关论文
共 61 条
[1]   Telomerase activity in germ cell cancers and mature teratomas [J].
Albanell, J ;
Bosl, GJ ;
Reuter, VE ;
Engelhardt, M ;
Franco, S ;
Moore, MAS ;
Dmitrovsky, E .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1999, 91 (15) :1321-1326
[2]   Telomeres and human disease: Ageing, cancer and beyond [J].
Blasco, MA .
NATURE REVIEWS GENETICS, 2005, 6 (08) :611-622
[3]   TERT promoter mutations and telomerase reactivation in urothelial cancer [J].
Borah, Sumit ;
Xi, Linghe ;
Zaug, Arthur J. ;
Powell, Natasha M. ;
Dancik, Garrett M. ;
Cohen, Scott B. ;
Costello, James C. ;
Theodorescu, Dan ;
Cech, Thomas R. .
SCIENCE, 2015, 347 (6225) :1006-1010
[4]   Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines [J].
Bryan, TM ;
Englezou, A ;
DallaPozza, L ;
Dunham, MA ;
Reddel, RR .
NATURE MEDICINE, 1997, 3 (11) :1271-1274
[5]   Modification of Enhancer Chromatin: What, How, and Why? [J].
Calo, Eliezer ;
Wysocka, Joanna .
MOLECULAR CELL, 2013, 49 (05) :825-837
[6]   Methylation of the TERT promoter and risk stratification of childhood brain tumours: an integrative genomic and molecular study [J].
Castelo-Branco, Pedro ;
Choufani, Sanaa ;
Mack, Stephen ;
Gallagher, Denis ;
Zhang, Cindy ;
Lipman, Tatiana ;
Zhukova, Nataliya ;
Walker, Erin J. ;
Martin, Dianna ;
Merino, Diana ;
Wasserman, Jonathan D. ;
Elizabeth, Cynthia ;
Alon, Noa ;
Zhang, Libo ;
Hovestadt, Volker ;
Kool, Marcel ;
Jones, David T. W. ;
Zadeh, Gelareh ;
Croul, Sidney ;
Hawkins, Cynthia ;
Hitzler, Johann ;
Wang, Jean C. Y. ;
Baruchel, Sylvain ;
Dirks, Peter B. ;
Malkin, David ;
Pfister, Stefan ;
Taylor, Michael D. ;
Weksberg, Rosanna ;
Tabori, Uri .
LANCET ONCOLOGY, 2013, 14 (06) :534-542
[7]  
Chapon C, 1997, RNA, V3, P1337
[8]   Suppression of the alternative lengthening of telomere pathway by the chromatin remodelling factor ATRX [J].
Clynes, David ;
Jelinska, Clare ;
Xella, Barbara ;
Ayyub, Helena ;
Scott, Caroline ;
Mitson, Matthew ;
Taylor, Stephen ;
Higgs, Douglas R. ;
Gibbons, Richard J. .
NATURE COMMUNICATIONS, 2015, 6
[9]   Telomerase activity is restored in human cells by ectopic expression of hTERT (hEST2), the catalytic subunit of telomerase [J].
Counter, CM ;
Meyerson, M ;
Eaton, EN ;
Ellisen, LW ;
Caddle, SD ;
Haber, DA ;
Weinberg, RA .
ONCOGENE, 1998, 16 (09) :1217-1222
[10]   Increasing incidence of thyroid cancer in the United States, 1973-2002 [J].
Davies, L ;
Welch, HG .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2006, 295 (18) :2164-2167