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La arquitectura genómica y transcriptómica de 2.000 tumores mamarios revela nuevos subgrupos en el seno
Christina Curtis1, Sohrab P Shah, Suet-Feung Chin
1Department of Oncology, University of Cambridge, Hills Road, Cambridge CB2 2XZ, UK.
Nature
|April 24, 2012
Resumen
Este estudio integra datos del genoma y el transcriptoma de casi 2.000 tumores de mama para identificar nuevos subgrupos moleculares. Las aberraciones del número de copias somáticas tienen un impacto significativo en la expresión génica, revelando nuevos impulsores del cáncer y resultados distintos para los pacientes.
Área de la Ciencia:
- Oncología Oncología.
- La genómica es la genómica.
- La transcriptómica es el campo de la transcripción.
Sus antecedentes:
- Comprender la heterogeneidad del cáncer de mama es crucial para las terapias dirigidas.
- El análisis genómico y transcriptómico integrado proporciona una visión más profunda de la biología del cáncer.
Objetivo del estudio:
- Para identificar nuevos subgrupos de cáncer de mama y los conductores moleculares utilizando perfiles integrados de ADN y ARN.
- Para asociar las aberraciones del número de copias con la expresión génica y los resultados clínicos.
Principales métodos:
- Análisis integrado del número de copias y los datos de expresión génica de 1.992 tumores mamarios primarios (conjuntos de descubrimiento y validación).
- Identificación de las aberraciones del número de copias (CNA) de acción cis y trans y su impacto en la expresión génica.
- Análisis no supervisado de perfiles de ADN-ARN emparejados para revelar nuevos subgrupos.
Principales resultados:
- Los CNA somáticos influyen en la expresión génica en aproximadamente el 40% de los genes, dominados por los CNA de acción cis y trans.
- Se identificaron nuevos genes cancerosos (por ejemplo, PPP2R2A, MTAP, MAP2K4) a través de valores atípicos de expresión impulsados por CNA.
- Se descubrieron nuevos subgrupos de cáncer de mama con resultados clínicos distintos, incluido un subgrupo de alto riesgo positivo para los receptores de estrógenos y un subgrupo de pronóstico favorable CNA-devoid.
- Los puntos calientes de aberración de acción trans caracterizados modulan redes específicas de subgrupos, como la respuesta inmune y las redes mitóticas.
Conclusiones:
- El análisis genómico y transcriptómico integrado revela una nueva estratificación molecular del cáncer de mama.
- Las CNA somáticas son los principales impulsores de la heterogeneidad de la expresión génica y definen distintos subgrupos clínicos.
- Este enfoque identifica nuevos objetivos terapéuticos y proporciona un marco para el tratamiento personalizado del cáncer de mama.
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