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.
Original language | English (US) |
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Pages (from-to) | 17-26 |
Number of pages | 10 |
Journal | Journal of Neuro-Oncology |
Volume | 119 |
Issue number | 1 |
DOIs | |
State | Published - Aug 2014 |
Keywords
- ALT
- ATRX
- Neuroblastoma
- Telomerase
- Telomere
- p53
ASJC Scopus subject areas
- Oncology
- Neurology
- Clinical Neurology
- Cancer Research