Journal Article

DKFZ-2021-00464

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Alternative lengthening of telomeres in childhood neuroblastoma from genome to proteome.

Hartlieb, S. (First author)DKFZ* ; Sieverling, L. (First author)DKFZ* ; Nadler-Holly, M. ; Ziehm, M. ; Toprak, U. H.DKFZ* ; Herrmann, C. ; Ishaque, N. ; Okonechnikov, K.DKFZ* ; Gartlgruber, M.DKFZ* ; Park, Y.-G.DKFZ* ; Wecht, E. M.DKFZ* ; Savelyeva, L.DKFZ* ; Henrich, K.-O.DKFZ* ; Rosswog, C. ; Fischer, M. ; Hero, B. ; Jones, D. T. W.DKFZ* ; Pfaff, E.DKFZ* ; Witt, O.DKFZ* ; Pfister, S. M.DKFZ* ; Volckmann, R. ; Koster, J. ; Kiesel, K.DKFZ* ; Rippe, K.DKFZ* ; Taschner-Mandl, S. ; Ambros, P. ; Brors, B.DKFZ* ; Selbach, M. ; Feuerbach, L.DKFZ* ; Westermann, F. (Last author)DKFZ*

2021
Nature Publishing Group UK [London]

This record in other databases:  

Please use a persistent id in citations: doi:10.1038/s41467-021-21247-8

Abstract: Telomere maintenance by telomerase activation or alternative lengthening of telomeres (ALT) is a major determinant of poor outcome in neuroblastoma. Here, we screen for ALT in primary and relapsed neuroblastomas (n = 760) and characterize its features using multi-omics profiling. ALT-positive tumors are molecularly distinct from other neuroblastoma subtypes and enriched in a population-based clinical sequencing study cohort for relapsed cases. They display reduced ATRX/DAXX complex abundance, due to either ATRX mutations (55%) or low protein expression. The heterochromatic histone mark H3K9me3 recognized by ATRX is enriched at the telomeres of ALT-positive tumors. Notably, we find a high frequency of telomeric repeat loci with a neuroblastoma ALT-specific hotspot on chr1q42.2 and loss of the adjacent chromosomal segment forming a neo-telomere. ALT-positive neuroblastomas proliferate slowly, which is reflected by a protracted clinical course of disease. Nevertheless, children with an ALT-positive neuroblastoma have dismal outcome.

Note: #EA:B087#EA:#B340#LA:B087#2021 Feb 24;12(1):1269

---

Contributing Institute(s):

1. B087 Neuroblastom Genomik (B087)
2. Angewandte Bioinformatik (B330)
3. DKTK HD zentral (HD01)
4. B062 Pädiatrische Neuroonkologie (B062)
5. KKE Pädiatrische Onkologie (B310)
6. B066 Chromatin-Netzwerke (B066)
7. Pediatric Glioma (B360)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2021

---

Database coverage:
; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 10 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

---