Complicated biallelic inactivation of Pten in radiation-induced mouse thymic lymphomas.
Mutat Res
; 686(1-2): 30-8, 2010 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-20060398
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
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Prevencao_e_fatores_de_risco
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Agentes_cancerigenos
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Tipos_de_cancer
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Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Alelos
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PTEN Fosfo-Hidrolase
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Leucemia-Linfoma Linfoblástico de Células T Precursoras
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Mutação
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Neoplasias Induzidas por Radiação
Limite:
Animals
Idioma:
En
Revista:
Mutat Res
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Japão