@misc{oai:repo.qst.go.jp:00071051,
 author = {Blyth, Benjamin and Kakinuma, Shizuko and Amasaki, Yoshiko and Shang, Yi and Sawai, Tomoko and Hirano, Shinobu and Tsuruoka, Chizuru and Nishimura, Mayumi and Shimada, Yoshiya and Ｂｌｙｔｈ Ｂｅｎｊａｍｉｎ and 柿沼 志津子 and 甘崎 佳子 and 尚 奕 and 澤井 知子 and 坂入 しのぶ and 鶴岡 千鶴 and 西村 まゆみ and 島田 義也},
 month = {Feb},
 note = {Secondary cancer risk following carbon ion radiotherapy is a key consideration for its use in children over conventional photon radiotherapy. Understanding not only the relative carcinogenic risk of carbon ion therapy, but also the potentially different carcinogenic mechanisms is a primary goal of the Radiobiology for Childrens Health Research Program at the National Institute of Radiological Sciences, Japan.
The research program has undertaken a large-scale study over the past 8 years, for which cohorts of irradiated B6C3F1 mice are followed throughout their natural life for tumour development. The study includes groups which vary in their age-at-exposure, as well as radiation source, quality, fractionation and total dose. From this study, a sub-cohort of mice was selected for detailed genetic analysis of radiation-induced thymic lymphomas. This included all mice irradiated with 4 - 4.8 Gy carbon ions starting at one week of age (either in a single exposure, or four weekly fractions), which had been sacrificed in a moribund state with a cause of death at autopsy of thymic lymphoma (n 102 mice). DNA and RNA were isolated from the corresponding thymic lymphoma tissue bank samples. 
Gross genomic changes at tumour suppressor loci including Pten, Bcl11b and Ikzf1(IKAROS family zinc finger 1) are being assessed by loss of heterozygosity (LOH) analysis using PCR, and amplicon sizing of sites polymorphic for sequence length between the B6 and C3H parental strains. Smaller genetic alterations are being further assessed by exon sequencing of Pten, Bcl11b and Ikzf1 to identify small insertions/deletions and point-mutations. The features observed in the carbon ion-irradiated sub-cohort will be compared to those in a reference population of tumours in mice irradiated with a corresponding regime of gamma-radiation. Preliminary results suggest universal LOH in all carbon ion radiation-induced thymic lymphomas at sites flanking Bcl11b (compared to only 69pc in gamma radiation-induced thymic lymphomas), and approximately twice the frequency of LOH at a site -4 kb downstream of Pten (90pc vs. 43pc). Mechanistic insight into carbon ion-induced carcinogenesis will be vital in assessing the long-term safety of carbon ion radiotherapy for children., 平成24年度「個体レベルでのがん研究支援活動」ワークショップ　個体レベルのがん研究による相乗効果　学術的インターラクションから創造へ},
 title = {Profiling Genetic Changes at Common Tumor Suppressor Loci in Carbon Ion Radiation-Induced Thymic Lymphomas},
 year = {2013}
}