Format

Send to

Choose Destination
Nat Genet. 2017 Mar;49(3):349-357. doi: 10.1038/ng.3781. Epub 2017 Jan 30.

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

Author information

1
The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.
2
Oncology Graduate School Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
3
Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
4
Department of Biostatistics, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
5
Department of Neuro-Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
6
Program in Biostatistics, Bioinformatics, and Systems Biology, the University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA.
7
Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas, USA.
8
Institute for Applied Cancer Science, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
9
Department of Bioinformatics and Computational Biology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
10
Biopathology Center, Nationwide Children's Hospital, Columbus, Ohio, USA.
11
Department of Cancer Biology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

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.

PMID:
28135248
PMCID:
PMC5571729
DOI:
10.1038/ng.3781
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center