@article{oai:repo.qst.go.jp:00047442,
 author = {Ｂｌｙｔｈ, Ｂｅｎｊａｍｉｎ and 柿沼, 志津子 and 砂押, 正章 and 甘崎, 佳子 and 坂入, しのぶ and 小川, 佳那依 and 白神, 綾奈 and 尚, 奕 and 鶴岡, 千鶴 and 西村, まゆみ and 島田, 義也 and Ｂｌｙｔｈ Ｂｅｎｊａｍｉｎ and 柿沼 志津子 and 砂押 正章 and 甘崎 佳子 and 坂入 しのぶ and 小川 佳那依 and 白神 綾奈 and 尚 奕 and 鶴岡 千鶴 and 西村 まゆみ and 島田 義也},
 issue = {6},
 journal = {PLOS ONE},
 month = {Jun},
 note = {Monitoring mice exposed to carbon ion radiotherapy provides an indirect method to evaluate the potential for second cancer induction in
normal tissues outside the radiotherapy target volume, since such estimates are not yet possible from historical patient data. Here, male
and female B6C3F1 mice were given single or fractionated whole-body exposure(s) to a monoenergetic carbon ion radiotherapy beam at
the Heavy Ion Medical Accelerator in Chiba, Japan, matching the radiation quality delivered to the normal tissue ahead of the tumour
volume (average linear energy transfer = 13 keV.μm-1) during patient radiotherapy protocols. The mice were monitored for the remainder
of their lifespan, and a large number of T cell lymphomas that arose in these mice were analysed alongside those arising following an
equivalent dose of 137Cs gamma ray-irradiation. Using genome-wide DNA copy number analysis to identify genomic loci involved in
radiation-induced lymphomagenesis and subsequent detailed analysis of Notch1, Ikzf1, Pten, Trp53 and Bcl11b genes, we compared the
genetic profile of the carbon ion- and gamma ray-induced tumours. The canonical set of genes previously associated with radiationinduced
T cell lymphoma was identified in both radiation groups. While the pattern of disruption of the various pathways was somewhat
different between the radiation types, most notably Pten mutation frequency and loss of heterozygosity flanking Bcl11b, the most striking
finding was the observation of large interstitial deletions at various sites across the genome in carbon ion-induced tumours, which were
only seen infrequently in the gamma ray-induced tumours analysed. If such large interstitial chromosomal deletions are a characteristic
lesion of carbon ion irradiation, even when using the low linear energy transfer radiation to which normal tissues are exposed in
radiotherapy patients, understanding the dose-response and tissue specificity of such DNA damage could prove key to assessing second
cancer risk in carbon ion radiotherapy patients.},
 pages = {e0130666-1--e0130666-24},
 title = {Genetic Analysis of T Cell Lymphomas in Carbon Ion-Irradiated Mice Reveals Frequent Interstitial Chromosome Deletions: Implications for Second Cancer Induction in Normal Tissues During Carbon Ion Radiotherapy},
 volume = {10},
 year = {2015}
}