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c-MYC is a radiosensitive locus in human breast cells

Wade, M. A.; Sunter, N. J.; Fordham, S. E.; Long, A.; Masic, D.; Russell, L. J.; Harrison, C. J.; Rand, V.; Elstob, C.; Bown, N.; Rowe, D.; Lowe, C.; Cuthbert, G.; Bennett, S.; Crosier, S.; Bacon, C. M.; Onel, K.; Scott, K.; Scott, D.; Travis, L. B.; May, F E B; Allan, J. M.

Authors

Profile image of Mark Wade

Dr Mark Wade M.Wade@hull.ac.uk
Senior Lecturer in Molecular Genetics

N. J. Sunter

S. E. Fordham

A. Long

D. Masic

L. J. Russell

C. J. Harrison

V. Rand

C. Elstob

N. Bown

D. Rowe

C. Lowe

G. Cuthbert

S. Bennett

S. Crosier

C. M. Bacon

K. Onel

K. Scott

D. Scott

L. B. Travis

F E B May

J. M. Allan



Abstract

Ionising radiation is a potent human carcinogen. Epidemiological studies have shown that adolescent and young women are at increased risk of developing breast cancer following exposure to ionising radiation compared with older women, and that risk is dose-dependent. Although it is well understood which individuals are at risk of radiation-induced breast carcinogenesis, the molecular genetic mechanisms that underlie cell transformation are less clear. To identify genetic alterations potentially responsible for driving radiogenic breast transformation, we exposed the human breast epithelial cell line MCF-10A to fractionated doses of X-rays and examined the copy number and cytogenetic alterations. We identified numerous alterations of c-MYC that included high-level focal amplification associated with increased protein expression. c-MYC amplification was also observed in primary human mammary epithelial cells following exposure to radiation. We also demonstrate that the frequency and magnitude of c-MYC amplification and c-MYC protein expression is significantly higher in breast cancer with antecedent radiation exposure compared with breast cancer without a radiation aetiology. Our data also demonstrate extensive intratumor heterogeneity with respect to c-MYC copy number in radiogenic breast cancer, suggesting continuous evolution at this locus during disease development and progression. Taken together, these data identify c-MYC as a radiosensitive locus, implicating this oncogenic transcription factor in the aetiology of radiogenic breast cancer.

Citation

Wade, M. A., Sunter, N. J., Fordham, S. E., Long, A., Masic, D., Russell, L. J., Harrison, C. J., Rand, V., Elstob, C., Bown, N., Rowe, D., Lowe, C., Cuthbert, G., Bennett, S., Crosier, S., Bacon, C. M., Onel, K., Scott, K., Scott, D., Travis, L. B., …Allan, J. M. (2015). c-MYC is a radiosensitive locus in human breast cells. Oncogene, 34(38), 4985-4994. https://doi.org/10.1038/onc.2014.427

Journal Article Type Article
Acceptance Date Nov 21, 2014
Online Publication Date Dec 22, 2014
Publication Date Sep 17, 2015
Deposit Date Feb 4, 2019
Publicly Available Date Feb 5, 2019
Journal Oncogene
Print ISSN 0950-9232
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 34
Issue 38
Pages 4985-4994
DOI https://doi.org/10.1038/onc.2014.427
Keywords Breast cancer
Public URL https://hull-repository.worktribe.com/output/1271203
Publisher URL https://www.nature.com/articles/onc2014427
Contract Date Feb 4, 2019

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©2014 Springer

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