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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

Journal of Neuro-Oncology volume 119, pages 17–26 (2014)Cite this article

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).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Cancer Center, Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX, USA

    Ahsan S. Farooqi & C. Patrick Reynolds

  2. Department of Pharmacology, Texas Tech University Health Sciences Center, Lubbock, TX, USA

    C. Patrick Reynolds

  3. Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA

    C. Patrick Reynolds

  4. Department of Pediatrics, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA

    C. Patrick Reynolds

  5. Children’s Cancer Research Unit, Kids Research Institute, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia

    Rebecca A. Dagg & Loretta M. S. Lau

  6. Spectrum Pharmaceuticals, Inc., Irvine, CA, USA

    L. Mi Rim Choi

  7. Department of Cell Biology, Southwestern Medical Center, University of Texas, Dallas, TX, USA

    Jerry W. Shay

  8. Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia

    Jerry W. Shay

  9. Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, NSW, Australia

    Loretta M. S. Lau

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  1. Ahsan S. Farooqi
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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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  • DOI: https://doi.org/10.1007/s11060-014-1456-8

Keywords

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