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Secuenciación y análisis multicelulares del cáncer colorrectal humano
Shuhui Bian1,2,3, Yu Hou1,2, Xin Zhou4
1Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100871, China.
Science (New York, N.Y.)
|December 1, 2018
Resumen
Este estudio introduce la multiómica de una sola célula para analizar la dinámica genómica, epigenómica y transcriptómica del cáncer colorrectal. Los patrones de desmetilación del ADN se correlacionan con la densidad de la heterocromatina, ofreciendo nuevas ideas sobre la evolución del cáncer.
Área de la Ciencia:
- En el campo de la oncología
- La genómica
- La epigenética
Sus antecedentes:
- El cáncer colorrectal (CRC) se caracteriza por inestabilidad genómica, anomalías epigenéticas y desregulación de la expresión génica.
- Falta el análisis simultáneo de estas características en la resolución de una sola célula.
- La heterogeneidad intratumoral en el CRC sigue siendo incompletamente entendida.
Objetivo del estudio:
- Analizar simultáneamente las características genómicas, epigenómicas y transcriptómicas del cáncer colorrectal en resolución de una sola célula.
- Investigar la heterogeneidad intratumoral más allá de los conceptos establecidos.
- Reconstruir linajes genéticos y rastrear su dinámica epigenómica y transcriptómica.
Principales métodos:
- Secuenciación multicelular optimizada.
- Muestreo multirregional de tumores primarios, linfáticos y de metástasis distantes.
- Análisis de la metilación del ADN en todo el genoma, la modificación de la histona H3K9me3 y la expresión génica.
Principales resultados:
- Los niveles de metilación del ADN en todo el genoma fueron consistentes dentro de los sublíneos genéticos.
- Se observaron patrones de desmetilación de ADN consistentes en todo el genoma en 10 pacientes.
- Los grados de desmetilación del ADN se correlacionan con las densidades de H3K9me3 asociadas a la heterocromatina y los elementos nucleares intercalados largos 1.
Conclusiones:
- La secuenciación multiómica unicelular es factible para reconstruir linajes genéticos en el cáncer colorrectal.
- La dinámica epigenómica y transcriptómica se puede rastrear dentro de estos linajes.
- Los patrones de desmetilación del ADN ofrecen información sobre la heterogeneidad y la evolución del cáncer colorrectal.
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