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

Floris P. Barthel, Wei Wei, Ming Tang, Emmanuel Martinez-Ledesma, Xin Hu, Samirkumar B. Amin, Kadir C. Akdemir, Sahil Seth, Xingzhi Song, Qianghu Wang, Tara Lichtenberg, Jian Hu, Jianhua Zhang, Siyuan Zheng, Roel G.W. Verhaak

Research output: Contribution to journalArticlepeer-review

185 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)349-357
Number of pages9
JournalNature Genetics
Volume49
Issue number3
DOIs
StatePublished - Mar 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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