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The effect of age at exposure on the inactivating mechanisms and relative contributions of key tumor suppressor genes in radiation-induced mouse T-cell lymphomas
https://repo.qst.go.jp/records/47345
https://repo.qst.go.jp/records/47345c1faa3bc-b9db-4576-9f32-a72e957574dd
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2016-01-18 | |||||
| タイトル | ||||||
| タイトル | The effect of age at exposure on the inactivating mechanisms and relative contributions of key tumor suppressor genes in radiation-induced mouse T-cell lymphomas | |||||
| 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 |
砂押, 正章
× 砂押, 正章× 甘崎, 佳子× 坂入, しのぶ× Ｂｌｙｔｈ, Ｂｅｎｊａｍｉｎ× 森岡, 孝満× 上西, 睦美× 尚, 奕× 西村, まゆみ× 島田, 義也× 立花, 章× 柿沼, 志津子× 砂押 正章× 甘崎 佳子× 坂入 しのぶ× Ｂｌｙｔｈ Ｂｅｎｊａｍｉｎ× 森岡 孝満× 上西 睦美× 尚 奕× 西村 まゆみ× 島田 義也× 立花 章× 柿沼 志津子 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Children are considered more sensitive to radiation-induced cancer than adults, yet any differences ingenomic alterations associated with age-at-exposure and their underlying mechanisms remain unclear.We assessed genome-wide DNA copy number and mutation of key tumor suppressor genes in T-celllymphomas arising after weekly irradiation of female B6C3F1 mice with 1.2 Gy X-rays for 4 consecutiveweeks starting during infancy (1 week old), adolescence (4 weeks old) or as young adults (8 weeks old).Although T-cell lymphoma incidence was similar, loss of heterozygosity at Cdkn2a on chromosome 4 andat Ikaros on chromosome 11 was more frequent in the two older groups, while loss at the Pten locus onchromosome 19 was more frequent in the infant-irradiated group. Cdkn2a and Ikaros mutation/loss wasa common feature of the young adult-irradiation group, with Ikaros frequently (50%) incurring multipleindependent hits (including deletions and mutations) or suffering a single hit predicted to result in adominant negative protein (such as those lacking exon 4, an isoform we have designated Ik12, whichlacks two DNA binding zinc-finger domains). Conversely, Pten mutations were more frequent after earlyirradiation (60%) than after young adult-irradiation (30%). Homozygous Pten mutations occurred withoutDNA copy number change after irradiation starting in infancy, suggesting duplication of the mutatedallele by chromosome mis-segregation or mitotic recombination. Our findings demonstrate that whiledeletions on chromosomes 4 and 11 affecting Cdkn2a and Ikaros are a prominent feature of young adultirradiation-induced T-cell lymphoma, tumors arising after irradiation from infancy suffer a second hit inPten by mis-segregation or recombination. This is the first report showing an influence of age-at-exposureon genomic alterations of tumor suppressor genes and their relative involvement in radiation-inducedT-cell lymphoma. These data are important for considering the risks associated with childhood exposureto radiation. | |||||
| 書誌情報 |
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 巻 779, p. 58-67, 発行日 2015-09 |
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| 出版者 | ||||||
| 出版者 | Elsevier Ltd. | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0027-5107 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1016/j.mrfmmm.2015.06.004 | |||||
