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Las firmas de las alteraciones del número de copias en el cáncer humano

Christopher D Steele¹, Ammal Abbasi^2,3,4, S M Ashiqul Islam^2,3,4

¹Research Department of Pathology, Cancer Institute, University College London, London, UK.

|June 15, 2022

Resumen

Los investigadores desarrollaron un nuevo marco para analizar las alteraciones del número de copias de ADN en 9.873 cánceres. Este marco identificó 21 firmas de número de copia distintas, revelando diversos procesos mutacionales subyacentes en los tumores humanos.

Área de la Ciencia:

Genómica y Biología del Cáncer
Biología computacional y bioinformática

Sus antecedentes:

Las alteraciones del número de copias del ADN (CNA) son comunes en el cáncer, que surgen del estrés de replicación, los errores mitóticos y los ciclos de ruptura-fusión-puente.
Las CNA contribuyen significativamente al inicio, la progresión y la resistencia al tratamiento del cáncer.
La comprensión de los patrones de CNA es crucial para descifrar el desarrollo del cáncer e identificar objetivos terapéuticos.

Objetivo del estudio:

Presentar un marco conceptual versátil para analizar los patrones de alteración del número de copias en diversos tipos de datos genómicos.
Aplicar este marco a una gran cohorte de cánceres humanos para identificar y caracterizar las firmas CNA.
Explorar las implicaciones biológicas y clínicas de las firmas de número de copia identificadas.

Principales métodos:

Desarrollo de un marco conceptual aplicable a la secuenciación de todo el genoma, la secuenciación de todo el exoma y otros datos de perfiles de ADN.
Aplicación del marco a 9.873 muestras de cáncer del Atlas del genoma del cáncer (TCGA) en 33 tipos de cáncer.
Análisis de los patrones de número de copias para identificar firmas mutacionales distintas.

Principales resultados:

Se identificó un conjunto de 21 firmas de número de copia, explicando el 97% de los patrones de CNA en las muestras analizadas.
Diecisiete firmas se vincularon con procesos biológicos conocidos como la duplicación de todo el genoma, la aneuploidia y la deficiencia de recombinación homóloga.
Quedan cuatro firmas de etiología inexplicable, y algunas están asociadas con ganancias de ADN extracromosómico y proto-oncogénico.

Conclusiones:

El marco desarrollado proporciona un enfoque unificado para el estudio de los ANC en varios tipos de datos y tipos de cáncer.
Las 21 firmas identificadas ofrecen una visión completa de los procesos mutacionales que impulsan la heterogeneidad del CNA en el cáncer humano.
Se necesita más investigación para aclarar los orígenes de las firmas de número de copia inexplicadas y su relevancia clínica.

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