@misc{oai:repo.qst.go.jp:00064181,
 author = {Takabatake, Takashi and Ishida, Yuka and Kakinuma, Shizuko and Doi, Kazutaka and Kaminishi, Mutsumi and Yamauchi, Kazumi and Kito, Seiji and Oota, Yuki and Moritake, Hiroyuki and Kokubo, Toshiaki and Nishimura, Mayumi and Nishikawa, Tetsu and Hino, Okio and Shimada, Yoshiya and 高畠 貴志 and 石田 有香 and 柿沼 志津子 and 土居 主尚 and 上西 睦美 and 山内 一己 and 鬼頭 靖司 and 太田 有紀 and 森竹 浩之 and 小久保 年章 and 西村 まゆみ and 西川 哲 and 島田 義也},
 month = {Dec},
 note = {Cancer risks of low-dose radiation are of great concern especially in relation to rapidly increasing medical exposures; however, their accurate assessments cope with many challenges and difficulties, partly due to inability to distinguish radiation-induced tumors from spontaneous ones.  Here, we analyzed dose-dependent effect of radiation on medulloblastoma development in Ptch1 heterozygous mice on C3B6F1 background.  The incidence and latency of medulloblastoma increased and shortened with increasing radiation dose, respectively (Fig. 1). Amazingly, radiation contributed tumorigenesis even at 50 mGy and 100 % of mice got medulloblastoma with 1.5 Gy.  Loss of heterozygosity (LOH) analysis on a total of 164 tumors (Fig. 2) indicated that spontaneous tumors showed LOH in broad regions on chromosome 13, including Ptch1 and distally-extending telomeric portion (S-type).  In contrast, tumors developed after 3 Gy irradiation exhibited interstitial losses around Ptch1 (R-type).  A clear dose-dependent increase in the proportion of R-type tumor at intermediate doses suggested R-type to be a reliable radiation signature (Fig. 3).  Array-CGH analysis indicated the R-type-specific copy-number reduction around Ptch1 and LOH-type-independent frequent gains of whole chromosome 6. Integrated expression microarray analysis indicated that expression levels of many genes within the altered genomic regions faithfully reflected the genomic copy-number changes.  Furthermore, it was also suggested that these expression changes in turn influenced on many other genes, such as Tgfb2 and Plagl2, on widespread genomic regions.  This is the first demonstration that radiation-induced tumors developed after low-dose irradiation can be characterized quite precisely by interstitial deletion of Ptch1 and by associated gene expression profile., KIDS workshop 2009 in NIRS - IAEA NIRS Joint Workshop & NIRS Symposium on Radiation Protection for Children},
 title = {Genomic Radiation Signature Illuminates Low-Dose Effects with Sharply Reflected Transcriptome in Ptch1-Deficient Medulloblastomas},
 year = {2009}
}