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Alternative lengthening of telomeres in neuroblastoma cell lines is associated with a lack of MYCN genomic amplification and with p53 pathway aberrations

Abstract

Alternative lengthening of telomeres (ALT) is a telomerase-independent telomere length maintenance mechanism that enables the unlimited proliferation of a subset of cancer cells. Some neuroblastoma (NB) tumors appear to maintain telomere length by activating ALT. Of 40 NB cell lines, we identified four potential ALT cell lines (CHLA-90, SK-N-FI, LA-N-6, and COG-N-291) that were telomerase-negative and had long telomeres (a feature of ALT cells). All four cell lines lacked MYCN amplification and were p53 non-functional upon irradiation. Two of these cell lines (CHLA-90 and SK-N-FI) were positive for C-circles (telomeric DNA circles) and ALT-associated promyelocytic leukemia nuclear bodies, both of which are phenotypic characteristics of ALT. Mutation of ATRX (associated with ALT in tumors) was only found in CHLA-90. Thus, the ALT phenotype in NB may not be limited to tumors with ATRX mutations but is associated with a lack of MYCN amplification and alterations in the p53 pathway.

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Acknowledgments

This work was supported by a Grant from the National Cancer Institute (CA82830; C. P. Reynolds), Cancer Prevention & Research Institute of Texas (RP 110763; C. P. Reynolds), and Cure Cancer Australia Foundation (L. Lau); by a Cancer Institute of New South Wales Clinical Research Fellowship, Australia (07/CRF/105; L Lau) and National Health and Medical Research Council Early Career Fellowship, Australia (APP1012500; L. Lau).

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The authors declare that they have no conflict of interest.

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Correspondence to Loretta M. S. Lau.

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Farooqi, A.S., Dagg, R.A., Choi, L.M.R. et al. Alternative lengthening of telomeres in neuroblastoma cell lines is associated with a lack of MYCN genomic amplification and with p53 pathway aberrations. J Neurooncol 119, 17–26 (2014). https://doi.org/10.1007/s11060-014-1456-8

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Keywords

  • Neuroblastoma
  • Telomere
  • Telomerase
  • ALT
  • p53
  • ATRX