Identification of circulating tumor DNA for the early detection of small-cell lung cancer
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Fecha
2016
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Publicado en
EBioMedicine, 2352-3964, Vol. 10, August, 2016, p.117-123
Publicado por
Elsevier
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Resumen
Descripción
Abstract
Circulating tumor DNA (ctDNA) is emerging as a key potential biomarker for post-diagnosis surveillance but it may also play a crucial role in the detection of pre-clinical cancer. Small-cell lung cancer (SCLC) is an excellent candidate for early detection given there are no successful therapeutic options for late-stage disease, and it displays almost universal inactivation of TP53. We assessed the presence of TP53 mutations in the cell-free DNA (cfDNA) extracted from the plasma of 51 SCLC cases and 123 non-cancer controls. We identified mutations using a pipeline specifically designed to accurately detect variants at very low fractions. We detected TP53 mutations in the cfDNA of 49% SCLC patients and 11.4% of non-cancer controls. When stratifying the 51 initial SCLC cases by stage, TP53 mutations were detected in the cfDNA of 35.7% early-stage and 54.1% late-stage SCLC patients. The results in the controls were further replicated in 10.8% of an independent series of 102 non-cancer controls. The detection of TP53 mutations in 11% of the 225 non-cancer controls suggests that somatic mutations in cfDNA among individuals without any cancer diagnosis is a common occurrence, and poses serious challenges for the development of ctDNA screening tests.
Palabras clave
Small-Cell lung cancer, TP53 mutations, Early detection, Screening
Keywords
Temáticas
Ácidos nucleicos libres de células
ADN tumoral circulante
Carcinoma pulmonar de células pequeñas
Genes supresores de tumor
Diagnóstico precoz
ADN tumoral circulante
Carcinoma pulmonar de células pequeñas
Genes supresores de tumor
Diagnóstico precoz