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Genomic and gene expression signatures of radiation in medulloblastomas after low-dose irradiation in Ptch1 heterozygous mice
https://repo.qst.go.jp/records/45897
https://repo.qst.go.jp/records/4589704744f3c-4110-4a32-95c9-a38ccdaeb527
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2010-09-27 | |||||
| タイトル | ||||||
| タイトル | Genomic and gene expression signatures of radiation in medulloblastomas after low-dose irradiation in Ptch1 heterozygous mice | |||||
| 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_6501 | |||||
| 資源タイプ | journal article | |||||
| 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 |
Ishida, Yuka
× Ishida, Yuka× Takabatake, Takashi× Kakinuma, Shizuko× Doi, Kazutaka× Yamauchi, Kazumi× Kaminishi, Mutsumi× Kito, Seiji× Oota, Yuki× Amasaki, Yoshiko× Moritake, Hiroyuki× Kokubo, Toshiaki× Nishimura, Mayumi× Nishikawa, Tetsu× Hino, Okio× Shimada, Yoshiya× 石田 有香× 高畠 貴志× 柿沼 志津子× 土居 主尚× 山内 一己× 上西 睦美× 鬼頭 靖司× 太田 有紀× 甘崎 佳子× 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 | 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. | |||||
| 書誌情報 |
Carcinogenesis 巻 31, 号 9, p. 1694-1701, 発行日 2010-07 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0143-3334 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1093/carcin/bgq145 | |||||
