@article{oai:repo.qst.go.jp:00045897,
 author = {Ishida, Yuka and Takabatake, Takashi and Kakinuma, Shizuko and Doi, Kazutaka and Yamauchi, Kazumi and Kaminishi, Mutsumi and Kito, Seiji and Oota, Yuki and Amasaki, Yoshiko and Moritake, Hiroyuki and Kokubo, Toshiaki and Nishimura, Mayumi and Nishikawa, Tetsu and Hino, Okio and Shimada, Yoshiya and 石田 有香 and 高畠 貴志 and 柿沼 志津子 and 土居 主尚 and 山内 一己 and 上西 睦美 and 鬼頭 靖司 and 太田 有紀 and 甘崎 佳子 and 小久保 年章 and 西村 まゆみ and 西川 哲 and 島田 義也},
 issue = {9},
 journal = {Carcinogenesis},
 month = {Jul},
 note = {Accurate cancer risk assessment of low-dose radiation poses many challenges that are partly due to the inability to distinguish radiation-induced tumors from spontaneous ones. To elucidate characteristic features of radiation-induced tumors, we analyzed 163 medulloblastomas that developed either spontaneously or after X-ray irradiation at doses of 0.05-3 Gy in Ptch1 heterozygous mice. All spontaneous tumors showed loss of heterozygosity in broad regions on chromosome 13, with losses at all consecutive markers distal to Ptch1 locus (S-type). In contrast, all tumors that developed after 3 Gy irradiation exhibited interstitial losses around Ptch1 with distal markers retained (R-type). There was a clear dose-dependent increase in the proportion of R-type tumors within the intermediate dose range, indicating that the R-type change is a reliable radiation signature. Importantly, the incidence of R-type tumors increased significantly (P = 0.007) at a dose as low as 50 mGy. Integrated array-comparative genomic hybridization and expression microarray analyses demonstrated that expression levels of many genes around the Ptch1 locus faithfully reflected the signature-associated reduction in genomic copy-number. Furthermore, 573 genes on other chromosomes were also expressed differently between S-type and R-type tumors. They include genes whose expression changes during early cerebellar development such as Plagl1 and Tgfb2, suggesting a recapitulation of gene subsets functioning at distinct developmental stages. These findings provide, for the first time, solid experimental evidence for a significant increase in cancer risk by low-dose radiation at diagnostic levels, and imply that radiation-induced carcinogenesis accompanies both genomic and gene expression signatures.},
 pages = {1694--1701},
 title = {Genomic and gene expression signatures of radiation in medulloblastomas after low-dose irradiation in Ptch1 heterozygous mice},
 volume = {31},
 year = {2010}
}