Telomere trimming and DNA damage as signatures of high risk neuroblastoma Journal Article


Authors: Yu, E. Y.; Cheung, I. Y.; Feng, Y.; Rabie, M. O.; Roboz, G. J.; Guzman, M. L.; Cheung, N. K. V.; Lue, N. F.
Article Title: Telomere trimming and DNA damage as signatures of high risk neuroblastoma
Abstract: Telomeres play important roles in genome stability and cell proliferation. High risk neuroblastoma (HRNB), an aggressive childhood cancer, is especially reliant on telomere maintenance. Three recurrent genetic aberrations in HRNB (MYCN amplification, TERT re-arrangements, and ATRX mutations)are mutually exclusive and each capable of promoting telomere maintenance mechanisms (i.e., through telomerase or ALT). We analyzed a panel of 5 representative HRNB cell lines and 30 HRNB surgical samples using assays that assess average telomere lengths, length distribution patterns, single-stranded DNA on the G- and C-strand, as well as extra-chromosomal circular telomeres. Our analysis pointed to substantial and variable degrees of telomere DNA damage in HRNB, including pervasive oxidative lesions. Moreover, unlike other cancers, neuroblastoma consistently harbored high levels of C-strand ssDNA overhangs and t-circles, which are consistent with active “telomere trimming”. This feature is observed in both telomerase- and ALT-positive tumors and irrespective of telomere length distribution. Moreover, evidence for telomere trimming was detected in normal neural tissues, raising the possibility that TMMs in HRNB evolved in the face of a canonical developmental program of telomere shortening. Telomere trimming by itself appears to distinguish neuroectodermal derived tumors from other human cancers, a distinguishing characteristic with both biologic and therapeutic implications. © 2019 The Authors
Journal Title: NeoPlasia
Volume: 21
Issue: 7
ISSN: 1522-8002
Publisher: Elsevier Science Inc.  
Date Published: 2019-07-01
Start Page: 689
End Page: 701
Language: English
DOI: 10.1016/j.neo.2019.04.002
PROVIDER: scopus
PMCID: PMC6535646
PUBMED: 31128432
DOI/URL:
Notes: Source: Scopus
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  1. Nai-Kong Cheung
    650 Cheung
  2. Irene Y Cheung
    96 Cheung
  3. Yi Feng
    15 Feng