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Genomic Radiation Signature Illuminates Low-Dose Effects with Sharply Reflected Transcriptome in Ptch1-Deficient Medulloblastomas
https://repo.qst.go.jp/records/64181
https://repo.qst.go.jp/records/641813989d2f9-f4d0-4e37-b822-2b1bbf1bed31
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2011-01-07 | |||||
| タイトル | ||||||
| タイトル | Genomic Radiation Signature Illuminates Low-Dose Effects with Sharply Reflected Transcriptome in Ptch1-Deficient Medulloblastomas | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Takabatake, Takashi
× Takabatake, Takashi× Ishida, Yuka× Kakinuma, Shizuko× Doi, Kazutaka× Kaminishi, Mutsumi× Yamauchi, Kazumi× Kito, Seiji× Oota, Yuki× Moritake, Hiroyuki× Kokubo, Toshiaki× Nishimura, Mayumi× Nishikawa, Tetsu× Hino, Okio× Shimada, Yoshiya× 高畠 貴志× 石田 有香× 柿沼 志津子× 土居 主尚× 上西 睦美× 山内 一己× 鬼頭 靖司× 太田 有紀× 森竹 浩之× 小久保 年章× 西村 まゆみ× 西川 哲× 島田 義也 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | 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. | |||||
| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | KIDS workshop 2009 in NIRS - IAEA NIRS Joint Workshop & NIRS Symposium on Radiation Protection for Children | |||||
| 発表年月日 | ||||||
| 日付 | 2009-12-16 | |||||
| 日付タイプ | Issued | |||||
