Identification of circulating tumor DNA for the early detection of small-cell lung cancer

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.

• Autores: Fernandez-Cuesta, Lynnette; Avogbe, Patrice Hodonou; Leblay, Noemie; Delhomme, Tiffany M.; Gaborieau, Valerie; Abedi-Ardekani, Behnoush; Chanudet, Estelle; Olivier, Magali; Zaridze, David; Mukeria, Anush; Vilensky, Marta; Holcatova, Ivana; Polesel, Jerry; Simonato, Lorenzo; Canova, Cristina; Lagiou, Pagona; Brambilla, Christian; Byrnes, Graham; Scelo, Ghislaine; Le Calvez-Kelm, Florence; McKay, James D.; Brennan, Paul; Brambilla, Elisabeth; Perdomo Lara, Sandra Janneth
• Fecha de publicación: 2016
• Institución: Universidad El Bosque
• Repositorio: Repositorio U. El Bosque
• Idioma: eng
• OAI Identifier: oai:repositorio.unbosque.edu.co:20.500.12495/1611
• Acceso en línea: http://hdl.handle.net/20.500.12495/1611; https://doi.org/10.1016/j.ebiom.2016.06.032
• Palabra clave: Small-Cell lung cancer; TP53 mutations; Early detection; Screening; Ácidos nucleicos libres de células; ADN tumoral circulante; Carcinoma pulmonar de células pequeñas; Genes supresores de tumor; Diagnóstico precoz
• License: Attribution-NonCommercial-NoDerivatives 4.0 International