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Interstitial chromosomal deletion of the tuberous sclerosis complex 2 locus is a signature for radiation-associated renal tumors in Eker rats
https://repo.qst.go.jp/records/78471
https://repo.qst.go.jp/records/78471e465faab-c8fd-4b82-966d-54188a6060f9
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2020-01-21 | |||||
| タイトル | ||||||
| タイトル | Interstitial chromosomal deletion of the tuberous sclerosis complex 2 locus is a signature for radiation-associated renal tumors in Eker rats | |||||
| 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 |
Inoue, Tatsuya
× Inoue, Tatsuya× Kokubo, Toshiaki× Daino, Kazuhiro× Yanagihara, Hiromi× Watanabe, Fumiko× Tsuruoka, Chizuru× Amasaki, Yoshiko× Morioka, Takamitsu× Shino, Homma-Takeda× Kobayashi, Toshiyuki× Hino, Okio× Shimada, Yoshiya× Kakinuma, Shizuko× Tatsuya, Inoue× Toshiaki, Kokubo× Kazuhiro, Daino× Hiromi, Yanagihara× Fumiko, Watanabe× Chizuru, Tsuruoka× Yoshiko, Amasaki× Takamitsu, Morioka× Shino, Takeda× Yoshiya, Shimada× Shizuko, Kakinuma |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Ionizing radiation can damage DNA and thus is a risk factor for cancer. Eker rats, which carry a heterozygous germline mutation in the tumor-suppressor gene Tsc2, are susceptible to radiation-induced renal carcinogenesis. However, the molecular mechanisms involved in Tsc2 inactivation are unclear. We subjected Fischer 344 × Eker (Long Evans Tsc2 ) F1 hybrid rats to gamma-irradiation (2 Gy) at gestational day 19 (GD19) or postnatal day 5 (PND5) and investigated the patterns of genomic alterations in the Tsc2 allele of renal tumors that developed at 1 year after irradiation (N = 24 tumors for GD19, N = 10 for PND5), in comparison with spontaneously developed tumors (N = 8 tumors). Gamma-irradiation significantly increased the multiplicity of renal tumors. The frequency of LOH at the chromosome 10q12 region, including the Tsc2 locus, was 38%, 29%, and 60% in renal carcinomas developed from the nonirradiated, GD19, and PND5 groups, respectively. Array CGH analysis revealed that the LOH patterns on chromosome 10 in renal carcinomas were classified into chromosomal missegregation, mitotic recombination and chromosomal deletion types. LOH of the interstitial chromosomal deletion type was observed only in radiation-associated carcinomas. Sequence analysis for the wild-type Tsc2 allele in the LOH-negative carcinomas identified deletions (nonirradiated: 26%; GD19: 21%) and base-substitution mutations (GD19: 4%). Reduced expression of Tsc2 was also observed in the majority of the LOH-negative carcinomas. Our results suggest that interstitial chromosomal deletion is a characteristic mutagenic event caused by ionizing radiation, and it may contribute to the assessment of radiation-induced cancer risk. | |||||
| 書誌情報 |
Cancer Science 巻 111, 号 3, p. 840-848, 発行日 2020-01 |
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| 出版者 | ||||||
| 出版者 | Wiley Publishing on behalf of the Japanese Cancer Association | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1347-9032 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 31925975 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1111/cas.14307 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://onlinelibrary.wiley.com/doi/full/10.1111/cas.14307 | |||||
