Transcriptomics

Dataset Information

3

Biallelic and complicated inactivation of Pten in radiation-induced mouse thymic lymphomas


ABSTRACT: Inactivation of Pten occurs by multiple mechanisms including epigenetic silencing, point mutations, insertion, and deletion, which are tissue dependent. Although frequent loss of heterozygosity around Pten locus and plausible involvement of epigenetic silencing have been reported in radiation-induced thymic lymphomas, the frequency of Pten inactivation and the spectrum of causal aberrations have not yet been extensively characterized. Here, we assessed the principal mode of inactivation by comprehensively analyzing expression and alterations of Pten gene in 23 radiation-induced thymic lymphomas developed in B6C3F1 mice. We found no evidence for methylation-associated silencing of Pten gene. Instead, we found complex structural abnormalities in 8 lymphomas (35%) that included missense and nonsense mutations, 1- and 3-bp insertions, and focal deletions. Sequencing of deletion breakpoints suggested that illegitimate V(D)J recombination and microhomology-mediated rearrangement were responsible for the focal deletions. Seven out of these 8 lymphomas had biallelic alterations, and 4 of them did not express any Pten protein. These aberrations of Pten were well coincided with downstream Akt phosphorylation on Ser473. In conclusion, Pten inactivation, which is frequently biallelic and is caused by a variety of structural abnormalities but not by epigenetic silencing, is involved in radiation-induced lymphomagenesis. Three thymic lymphomas were analyzed by array-CGH method.

ORGANISM(S): Mus musculus  

SUBMITTER: Mayumi Nishimura   Yi Shang  Yoshiro Kobayashi  Yoshiya Shimada  Tomoko Miyoshi-Imamura  Yu Yamaguchi  Shizuko Kakinuma  Hiroyuki Nogawa  Takashi Takabatake  Kazumi Yamauchi  Tatsuhiko Imaoka  Yoshiko Amasaki 

PROVIDER: E-GEOD-17751 | ArrayExpress | 2010-05-06

SECONDARY ACCESSION(S): GSE17751PRJNA118355

REPOSITORIES: GEO, ArrayExpress

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Publications


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 ass  ...[more]

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