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Complicated biallelic inactivation of Pten in radiation-induced mouse thymic lymphomas
https://repo.qst.go.jp/records/45779
https://repo.qst.go.jp/records/457797d597236-147c-4881-ae6e-7b073a5f0a29
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2010-04-06 | |||||
| タイトル | ||||||
| タイトル | Complicated biallelic inactivation of Pten in radiation-induced mouse thymic 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 |
Yamaguchi, Yu
× Yamaguchi, Yu× Takabatake, Takashi× Kakinuma, Shizuko× Amasaki, Yoshiko× Nishimura, Mayumi× Imaoka, Tatsuhiko× Yamauchi, Kazumi× Shang, Yi× Miyoshi-Imamura, Tomoko× Nogawa, Hiroyuki× Kobayashi, Yoshiro× Shimada, Yoshiya× 山口 悠× 高畠 貴志× 柿沼 志津子× 甘崎 佳子× 西村 まゆみ× 今岡 達彦× 山内 一己× 尚 奕× 今村 智子× 島田 義也 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Inactivation of the phosphatase and tensin homolog gene (Pten) occurs via multiple tissue-dependent mechanisms including epigenetic silencing, point mutations, insertions, and deletions. Although frequent loss of heterozygosity around the Pten locus and plausible involvement of epigenetic silencing have been reported in radiation-induced thymic lymphomas, the proportion of lymphomas with inactivated Pten and the spectrum of causal aberrations have not been extensively characterized. Here, we assessed the mode of Pten inactivation by comprehensive analysis of the expression and alteration of Pten in 23 radiation-induced thymic lymphomas developed in B6C3F1 mice. We found no evidence for methylation-associated silencing of Pten; rather, complex structural abnormalities comprised of missense and nonsense mutations, 1- and 3-bp insertions, and focal deletions were identified in 8 of 23 lymphomas (35%). Sequencing of deletion breakpoints suggested that aberrant V(D)J recombination and microhomology-mediated rearrangement were responsible for the focal deletions. Seven of the 8 lymphomas had biallelic alterations, and 4 of them did not express Pten protein. These Pten aberrations coincided with downstream Akt phosphorylation. In conclusion, we demonstrate that Pten inactivation is frequently biallelic and is caused by a variety of structural abnormalities (rather than by epigenetic silencing) and is involved in radiation-induced lymphomagenesis. | |||||
| 書誌情報 |
Fundamental and Molecular Mechanisms of Mutagenesis : A Section of Mutation Research 巻 686, 号 1/2, p. 30-38, 発行日 2010-01 |
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| 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.2009.12.011 | |||||
