@article{oai:repo.qst.go.jp:00045779,
 author = {Yamaguchi, Yu and Takabatake, Takashi and Kakinuma, Shizuko and Amasaki, Yoshiko and Nishimura, Mayumi and Imaoka, Tatsuhiko and Yamauchi, Kazumi and Shang, Yi and Miyoshi-Imamura, Tomoko and Nogawa, Hiroyuki and Kobayashi, Yoshiro and Shimada, Yoshiya and 山口 悠 and 高畠 貴志 and 柿沼 志津子 and 甘崎 佳子 and 西村 まゆみ and 今岡 達彦 and 山内 一己 and 尚 奕 and 今村 智子 and 島田 義也},
 issue = {1/2},
 journal = {Fundamental and Molecular Mechanisms of Mutagenesis : A Section of Mutation Research},
 month = {Jan},
 note = {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.},
 pages = {30--38},
 title = {Complicated biallelic inactivation of Pten in radiation-induced mouse thymic lymphomas},
 volume = {686},
 year = {2010}
}