Journal of Neuro-Oncology

, Volume 119, Issue 1, pp 17–26 | Cite as

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

  • Ahsan S. Farooqi
  • Rebecca A. Dagg
  • L. Mi Rim Choi
  • Jerry W. Shay
  • C. Patrick Reynolds
  • Loretta M. S. LauEmail author
Laboratory Investigation


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.


Neuroblastoma Telomere Telomerase ALT p53 ATRX 



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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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Ahsan S. Farooqi
    • 1
  • Rebecca A. Dagg
    • 5
  • L. Mi Rim Choi
    • 6
  • Jerry W. Shay
    • 7
    • 8
  • C. Patrick Reynolds
    • 1
    • 2
    • 3
    • 4
  • Loretta M. S. Lau
    • 5
    • 9
    Email author
  1. 1.Cancer Center, Department of Cell Biology and BiochemistryTexas Tech University Health Sciences CenterLubbockUSA
  2. 2.Department of PharmacologyTexas Tech University Health Sciences CenterLubbockUSA
  3. 3.Department of Internal MedicineTexas Tech University Health Sciences CenterLubbockUSA
  4. 4.Department of Pediatrics, School of MedicineTexas Tech University Health Sciences CenterLubbockUSA
  5. 5.Children’s Cancer Research Unit, Kids Research InstituteThe Children’s Hospital at WestmeadWestmeadAustralia
  6. 6.Spectrum Pharmaceuticals, Inc.IrvineUSA
  7. 7.Department of Cell Biology, Southwestern Medical CenterUniversity of TexasDallasUSA
  8. 8.Center of Excellence in Genomic Medicine ResearchKing Abdulaziz UniversityJeddahSaudi Arabia
  9. 9.Discipline of Paediatrics and Child Health, Sydney Medical SchoolUniversity of SydneySydneyAustralia

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