Biopsia líquida identifica pacientes con cáncer de mama avanzado.

Se ha desarrollado un nuevo análisis de sangre que mide los cambios genéticos en el ADN del cáncer circulante que podría ayudar a identificar a los pacientes con cáncer de mama metastásico que podrían beneficiarse de un cambio de tratamiento.

El análisis de mutaciones somáticas de los tejidos tumorales de mama ha identificado una serie de subtipos moleculares de cáncer de mama distintos, caracterizados por diversas mutaciones somáticas, incluyendo las variantes de un solo nucleótido (SNV) y las alteraciones en el número de copias (CNA).

Científicos de la Universidad de Leicester (Leicester, Reino Unido) reclutaron a 42 pacientes con cáncer de mama metastásico, confirmado radiológicamente (MBC, por sus siglas en inglés) y a nueve mujeres que asistieron a la consulta de mamografía como parte de su control rutinario, como controles de edad correspondiente. Se recogieron muestras de sangre y se procesó el plasma utilizando el kit de Ácidos Nucleicos Circulantes (Qiagen, Hilden, Alemania).

El equipo diseñó un panel personalizado de 158-amplicones (rango de tamaño 125-175 pb) cubriendo 16 genes con base en estudios previos y bases de datos públicamente disponibles. La preparación de la biblioteca y la secuenciación con la Máquina de Genoma Personal (PGM), se realizaron usando el kit de preparación de la biblioteca Ion Ampliseq (Thermo Fisher Scientific, Waltham, MA, EUA). Se utilizó la reacción digital en cadena de la polimerasa de gotitas (ddPCR) para validar las mutaciones en la proteína tumoral p53 (TP53), en la subunidad alfa de la fosfatidilinositol-4,5-bisfosfato 3-quinasa (PIK3CA) y el receptor de estrógeno 1 (ESR1).

Los científicos no identificaron mutaciones en el ADN libre de células (cfADN) de los controles sanos, mientras que exactamente la mitad de las pacientes con cáncer de mama metastásico tenía al menos una mutación o amplificación en el cfADN (media 2, rango 1-6) en un total de 13 genes. El seguimiento longitudinal mostró cambios dinámicos en las mutaciones y la amplificación génica en el cfADN, indicando una respuesta clonal y subclonal al tratamiento que era más dinámica que la observada para el antígeno de cáncer 15-3 (CA15-3).

Al momento de la toma de la muestra se presentó progresión de la enfermedad en siete pacientes que mostraban amplificación del gen del receptor de la tirosina quinasa 2 (ERBB2) en su cfADN y tres de estas pacientes eran negativas al diagnóstico, sugiriendo una evolución clonal a un fenotipo más agresivo. Seis de las mujeres con cáncer hormonal tenían mutaciones en el gen ESR1, que se ha relacionado con la resistencia a los tratamientos anti-hormonales.

David Guttery, autor principal del estudio, dijo: “Hemos desarrollado un nuevo análisis de sangre que puede detectar simultáneamente mutaciones somáticas y copiar las alteraciones numéricas que son fundamentales en promover el crecimiento del cáncer de mama. A través del análisis del plasma sanguíneo y la medición de los cambios específicos del cáncer a los genes clave del cáncer de mama, incluyendo el HER2 y los genes del receptor de estrógeno, esperamos que esta prueba podría ayudar a los médicos y a las pacientes a elegir el mejor tratamiento en el mejor momento”. El estudio fue descrito por la profesora Jacqui A. Shaw, PhD, en una presentación oral en la Frank May Prize Lecture el 26 de junio de 2017, en la Universidad de Leicester.

 

Fuente: https://www.labmedica.es

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19 Octubre, 2017
Bioreferencia

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