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Nature ; 463(7283): 899-905, 2010 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-20164920

RESUMEN

A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-kappaBeta pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types.


Asunto(s)
Variaciones en el Número de Copia de ADN/genética , Dosificación de Gen/genética , Neoplasias/genética , Apoptosis/genética , Línea Celular Tumoral , Supervivencia Celular/genética , Amplificación de Genes/genética , Genómica , Humanos , Familia de Multigenes/genética , Proteína 1 de la Secuencia de Leucemia de Células Mieloides , Neoplasias/clasificación , Neoplasias/patología , Proteínas Proto-Oncogénicas c-bcl-2/genética , Transducción de Señal , Proteína bcl-X/genética
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