Synapse - Genomic footprints of activated telomere maintenance mechanisms in cancer

Genomic footprints of activated telomere maintenance mechanisms in cancer Journal Article

Authors:	Sieverling, L.; Hong, C.; Koser, S. D.; Ginsbach, P.; Kleinheinz, K.; Hutter, B.; Braun, D. M.; Cortés-Ciriano, I.; Xi, R.; Kabbe, R.; Park, P. J.; Eils, R.; Schlesner, M.; PCAWG-Structural Variation Working Group; Brors, B.; Rippe, K.; Jones, D. T. W.; Feuerbach, L.; & PCAWG Consortium
Contributors:	Abeshouse, A.; Al-Ahmadie, H.; Armenia, J.; Chen, H. W.; Davidson, N. R.; Gao, J.; Ghossein, R.; Giri, D. D.; Gundem, G.; Heins, Z.; Huse, J.; Iacobuzio-Donahue, C. A.; Kahles, A.; King, T. A.; Kundra, R.; Lehmann, K. V.; Levine, D. A.; Liu, E. M.; Ochoa, A.; Pastore, A.; Rätsch, G.; Reis-Filho, J.; Reuter, V.; Roehrl, M. H. A.; Sanchez-Vega, F.; Sander, C.; Schultz, N.; Senbabaoglu, Y.; Singer, S.; Socci, N. D.; Stark, S. G.; Vázquez-García, I.; Yellapantula, V. D.; Zhang, H.
Article Title:	Genomic footprints of activated telomere maintenance mechanisms in cancer
Abstract:	Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer. © 2020, The Author(s).
Keywords:	osteosarcoma; controlled study; gene mutation; major clinical study; single nucleotide polymorphism; somatic mutation; case control study; genetics; mutation; case-control studies; liver cell carcinoma; pancreas cancer; glioma; neoplasm; neoplasms; chromosome; telomere; dna damage; melanoma; prevalence; cohort analysis; genetic association; bladder cancer; telomerase; tumor marker; renal cell carcinoma; carcinogenesis; colorectal carcinoma; dna; glioblastoma; human genome; medulloblastoma; telomerase reverse transcriptase; cell cycle arrest; genomics; bile duct carcinoma; heterozygosity loss; cancer control; leiomyosarcoma; tumor; checkpoint kinase 1; stomach adenocarcinoma; transitional cell carcinoma; repetitive sequences, nucleic acid; genetic marker; nucleotide repeat; genome, human; liposarcoma; bone cancer; pancreas islet cell tumor; chaperone; molecular pathology; copy number variation; molecular chaperones; daxx protein; pilocytic astrocytoma; corepressor protein; tert protein, human; atrx protein, human; telomere homeostasis; chromothripsis; co-repressor proteins; cancer; humans; human; article; whole genome sequencing; long untranslated rna; malignant neoplasm; rna, long noncoding; transcriptional regulator atrx; daxx protein, human; x-linked nuclear protein
Journal Title:	Nature Communications
Volume:	11
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Date Published:	2020-02-05
Start Page:	733
Language:	English
DOI:	10.1038/s41467-019-13824-9
PUBMED:	32024817
PROVIDER:	scopus
PMCID:	PMC7002710
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85079058593&doi=10.1038%2fs41467-019-13824-9&partnerID=40&md5=3e1f4065f0e96e34be9b85a955b34c5b
Notes:	Article -- Erratum issued, see DOI: 10.1038/s41467-022-32328-7 -- Export Date: 13 January 2023 -- Source: Scopus