Recurrent hemizygous deletions in cancers may optimize proliferative potential.
Science
; 337(6090): 104-9, 2012 Jul 06.
Article
em En
| MEDLINE
| ID: mdl-22628553
ABSTRACT
Tumors exhibit numerous recurrent hemizygous focal deletions that contain no known tumor suppressors and are poorly understood. To investigate whether these regions contribute to tumorigenesis, we searched genetically for genes with cancer-relevant properties within these hemizygous deletions. We identified STOP and GO genes, which negatively and positively regulate proliferation, respectively. STOP genes include many known tumor suppressors, whereas GO genes are enriched for essential genes. Analysis of their chromosomal distribution revealed that recurring deletions preferentially overrepresent STOP genes and underrepresent GO genes. We propose a hypothesis called the cancer gene island model, whereby gene islands encompassing high densities of STOP genes and low densities of GO genes are hemizygously deleted to maximize proliferative fitness through cumulative haploinsufficiencies. Because hundreds to thousands of genes are hemizygously deleted per tumor, this mechanism may help to drive tumorigenesis across many cancer types.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transformação Celular Neoplásica
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Deleção de Sequência
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Proliferação de Células
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Genes Neoplásicos
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Haploinsuficiência
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Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos