Chronic radiation exposure of neuroblastoma cells reduces nMYC copy number

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

doi:10.3892/ol.2017.6652

Chronic radiation exposure of neuroblastoma cells reduces nMYC copy number

Authors:
- Manu Gnanamony
- Reuben Antony
- Karen S. Fernández
- Libes Jaime
- Julian Lin
- Pushpa A. Joseph
- Christopher S. Gondi
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Affiliations: Department of Pediatrics, University of Illinois College of Medicine, Peoria, IL 61605, USA, UC Davis Comprehensive Cancer Center, Pediatric Hematology and Oncology, UC Davis Children's Hospital, Sacramento, CA 95817, USA, Cancer and Blood Diseases Center, 9300 Valley Children's Place FC13, Madera, CA 93636, USA, Department of Neurosurgery, University of Illinois College of Medicine, Peoria, IL 61605, USA, Department of Pathology, University of Illinois College of Medicine, Peoria, IL 61605, USA
Published online on: July 21, 2017 https://doi.org/10.3892/ol.2017.6652
Pages: 3363-3370
Copyright: © Gnanamony et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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