학술논문
Identification of Circulating Tumor DNA for the Early Detection of Small-cell Lung Cancer
Document Type
article
Author
Lynnette Fernandez-Cuesta; Sandra Perdomo; Patrice H. Avogbe; Noemie Leblay; Tiffany M. Delhomme; Valerie Gaborieau; Behnoush Abedi-Ardekani; Estelle Chanudet; Magali Olivier; David Zaridze; Anush Mukeria; Marta Vilensky; Ivana Holcatova; Jerry Polesel; Lorenzo Simonato; Cristina Canova; Pagona Lagiou; Christian Brambilla; Elisabeth Brambilla; Graham Byrnes; Ghislaine Scelo; Florence Le Calvez-Kelm; Matthieu Foll; James D. McKay; Paul Brennan
Source
EBioMedicine, Vol 10, Iss C, Pp 117-123 (2016)
Subject
Language
English
ISSN
2352-3964
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.