Caracterización molecular por secuenciación de nueva generación obtenida en biopsia líquida en una cohorte multicéntrica de pacientes con diagnóstico de cáncer de pulmón avanzado en Argentina

Martina Spotti; José N. Minatta; Manglio M. Rizzo; Nicolás Castagneris; Susana Sena; Gonzalo Recondo; María Virginia Bluthgen

doi:10.56969/oc.v27i2.79

Autores/as

Martina Spotti Servicio de Oncología Clínica, Hospital Alemán de Buenos Aires https://orcid.org/0000-0002-7618-5684
José N. Minatta Hospital Italiano, Buenos Aires https://orcid.org/0000-0002-3531-1920
Manglio M. Rizzo Servicio de Oncología Clínica, Hospital Universitario Austral, Buenos Aires https://orcid.org/0000-0003-2829-4701
Nicolás Castagneris Servicio de Oncología, Clínica Universitaria Reina Fabiola, Córdoba
Susana Sena Hospital Alemán, Buenos Aires https://orcid.org/0000-0002-4511-6395
Gonzalo Recondo (H) Servicio de Oncología, CEMIC, Buenos Aires https://orcid.org/0000-0002-0127-1019
María Virginia Bluthgen Servicio de Oncología Clínica, Hospital Alemán de Buenos Aires https://orcid.org/0000-0001-5343-218X

DOI:

https://doi.org/10.56969/oc.v27i2.79

Palabras clave:

secuenciación de nueva generación, biopsia líquida, cáncer de pulmón de células no pequeñas, next-generation sequencing, liquid biopsy, non-small cell lung cancer

Resumen

La secuenciación de nueva generación (NGS) ha revolucionado el diagnóstico molecular del cáncer de pulmón. A pesar que el tejido tumoral ha sido históricamente el bioespecimen estándar, éste tiene algunas limitaciones. La biopsia líquida representa una alternativa no invasiva, práctica y reproducible para la genotipificación del cáncer de pulmón de células no pequeñas (CPCNP). Se presenta la caracterización molecular por NGS en plasma, descripción de alteraciones moleculares en genes potencialmente accionables y genes de potencial origen germinal y variantes potencialmente involucradas en el proceso de hematopoyesis clonal. Análisis retrospectivo, observacional, multicéntrico de cohorte de pacientes con diagnóstico de CPCNP no escamoso avanzado de 5 hospitales universitarios de Argentina a los que se les realizó biopsia líquida (FoundationLiquidCDx) entre junio y diciembre 2020. Se realizó la caracterización de oncogenicidad y accionabilidad según OncoKB, COSMIC y VarSome. Se incluyeron 52 pacientes; 43 muestras al diagnóstico y 9 a la progresión. La mediana de carga mutacional tumoral fue 3 mut/mb [0-172] en 39 muestras evaluables; inestabilidad microsatelital en 1 de 3 muestras evaluables. Se identificaron 254 alteraciones moleculares en 80 genes (n=50) y 33 alteraciones en 13 genes potencialmente accionables en el 49% de los pacientes (21/43) siendo las más frecuentes: KRAS 18.6% (8/43), NF1 11.6% (5/43) y EGFR 9.3% (4/43). Se identificaron 13 alteraciones con valor de frecuencia alélica > 40% en genes de potencial origen germinal (BRCA1, BRCA2, TP53, CSF3R y CHEK2). Este análisis aporta una descripción de la genotipificación por NGS en biopsia líquida de una cohorte de pacientes nuestra población.

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