Chronic radiation exposure of neuroblastoma cells reduces nMYC copy number

Manu Gnanamony, Reuben Antony, Karen S. Fernández, Libes Jaime, Julian Lin, Pushpa A. Joseph, Christopher S. Gondi

Research output: Contribution to journalArticle

Abstract

Neuroblastoma accounts for >15% of cancer–associated mortalities of children in the USA. Despite aggressive treatment regimens, the long–term survival for these children remains <40%. The identification of v–Myc avian myelocytomatosis viral oncogene neuroblastoma–derived homolog (nMYC) gene amplification during diagnosis is associated with poor prognosis in neuroblastoma. There are limited studies examining changes in nMYC copy numbers in response to therapy and its biological effect on cancer cells. The aim of the present study was to evaluate the effect of radiation on nMYC expression and amplification status in high–risk neuroblastoma. The effect of acute (5 Gy) and chronic (25 Gy) radiation on two nMYC–amplified cell lines, SK–N–BE (2) and NB–1691, was investigated. The results demonstrate that, following chronic but not acute radiation, the two cell lines regained their proliferation potential similar to the controls. This increased proliferation was characterized by loss of nMYC mRNA and protein expression. It was also revealed that nMYC loss was accompanied by nuclear localization of c–Myc. Using fluorescent in situ hybridization and quantitative polymerase chain reaction analysis, the results of the present study demonstrated that chronic radiation causes a severe loss of nMYC gene copy number. The present study is the first to provide experimental evidence that prolonged radiation therapy affects nMYC gene copy number in high–risk neuroblastoma but does not significantly improve the prognostic outlook.

Original languageEnglish (US)
Pages (from-to)3363-3370
Number of pages8
JournalOncology Letters
Volume14
Issue number3
DOIs
StatePublished - Jan 1 2017

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Keywords

  • Copy number
  • Neuroblastoma
  • Radiation
  • v-Myc avian myelocytomatosis viral oncogene neuroblastoma-derived homolog

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Gnanamony, M., Antony, R., Fernández, K. S., Jaime, L., Lin, J., Joseph, P. A., & Gondi, C. S. (2017). Chronic radiation exposure of neuroblastoma cells reduces nMYC copy number. Oncology Letters, 14(3), 3363-3370. https://doi.org/10.3892/ol.2017.6652