AID produces DNA double-strand breaks in non-Ig genes and mature B cell lymphomas with reciprocal chromosome translocations.
Mol Cell
; 36(4): 631-41, 2009 Nov 25.
Article
em En
| MEDLINE
| ID: mdl-19941823
ABSTRACT
Cancer-initiating translocations such as those associated with lymphomas require the formation of paired DNA double-strand breaks (DSBs). Activation-induced cytidine deaminase (AID) produces widespread somatic mutation in mature B cells; however, the extent of "off-target" DSB formation and its role in translocation-associated malignancy is unknown. Here, we show that deregulated expression of AID causes widespread genome instability, which alone is insufficient to induce B cell lymphoma; transformation requires concomitant loss of the tumor suppressor p53. Mature B cell lymphomas arising as a result of deregulated AID expression are phenotypically diverse and harbor clonal reciprocal translocations involving a group of Immunoglobulin (Ig) and non-Ig genes that are direct targets of AID. This group includes miR-142, a previously unknown micro-RNA target that is translocated in human B cell malignancy. We conclude that AID produces DSBs throughout the genome, which can lead to lymphoma-associated chromosome translocations in mature B cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Translocação Genética
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Genes de Imunoglobulinas
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Linfoma de Células B
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Citidina Desaminase
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Cromossomos de Mamíferos
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Quebras de DNA de Cadeia Dupla
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article