title: Systematic analysis of telomere length and somatic alterations in 31 cancer types.
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.
authors.affiliation: The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.|Oncology Graduate School Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.|Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Floris P
authors.initials: FP
authors.lastname: Barthel
authors.affiliation: Department of Biostatistics, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ming
authors.identifier: http://orcid.org/0000-0002-7739-8913
authors.initials: M
authors.lastname: Tang
authors.affiliation: Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Department of Neuro-Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Martinez-Ledesma
authors.affiliation: Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Program in Biostatistics, Bioinformatics, and Systems Biology, the University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Samirkumar B
authors.initials: SB
authors.lastname: Amin
authors.affiliation: Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Kadir C
authors.initials: KC
authors.lastname: Akdemir
authors.affiliation: Institute for Applied Cancer Science, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Sahil
authors.identifier: http://orcid.org/0000-0003-4579-3959
authors.initials: S
authors.lastname: Seth
authors.affiliation: Institute for Applied Cancer Science, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Xingzhi
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Department of Bioinformatics and Computational Biology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Qianghu
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Biopathology Center, Nationwide Children's Hospital, Columbus, Ohio, USA.
authors.forename: Tara
authors.initials: T
authors.lastname: Lichtenberg
authors.affiliation: Department of Cancer Biology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Hu
authors.affiliation: Institute for Applied Cancer Science, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Department of Neuro-Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Siyuan
authors.identifier: http://orcid.org/0000-0002-7176-5348
authors.initials: S
authors.lastname: Zheng
authors.affiliation: The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.|Department of Genomic Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Department of Bioinformatics and Computational Biology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Roel G W
authors.initials: RG
authors.lastname: Verhaak
mesh_terms: D019175:DNA Methylation / Q000235:genetics; D005910:Glioma / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D056286:Retinoblastoma Binding Proteins / Q000235:genetics; D012509:Sarcoma / Q000235:genetics; D019098:Telomerase / Q000235:genetics; D016615:Telomere / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: C000606393:RB1 protein, human; D056286:Retinoblastoma Binding Proteins; D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases; D019098:Telomerase