Identification of Circulating Tumor DNA for the Early Detection of Small-cell Lung Cancer
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.
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BibTeX
@article{fernandezcuesta2026identification,
title = {{Identification of Circulating Tumor DNA for the Early Detection of Small-cell Lung Cancer}},
author = {Lynnette Fernandez-Cuesta and Sandra Perdomo and Patrice H Avogbe and Noemie Leblay and Tiffany M Delhomme and Valerie Gaborieau and Behnoush Abedi-Ardekani and Estelle Chanudet and Magali Olivier and David Zaridze and Anush Mukeria and Marta Vilensky and Ivana Holcatova and Jerry Polesel and Lorenzo Simonato and Cristina Canova and Pagona Lagiou and Christian Brambilla and Elisabeth Brambilla and Graham Byrnes and Ghislaine Scelo and Florence Le Calvez-Kelm and Matthieu Foll and James D Mckay and Paul Brennan},
journal = {EBioMedicine},
year = {2026},
month = oct,
doi = {10.1016/j.ebiom.2016.06.032},
url = {https://hal.science/hal-05842798v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Identification of Circulating Tumor DNA for the Early Detection of Small-cell Lung Cancer
AU - Lynnette Fernandez-Cuesta
AU - Sandra Perdomo
AU - Patrice H Avogbe
AU - Noemie Leblay
AU - Tiffany M Delhomme
AU - Valerie Gaborieau
AU - Behnoush Abedi-Ardekani
AU - Estelle Chanudet
AU - Magali Olivier
AU - David Zaridze
AU - Anush Mukeria
AU - Marta Vilensky
AU - Ivana Holcatova
AU - Jerry Polesel
AU - Lorenzo Simonato
AU - Cristina Canova
AU - Pagona Lagiou
AU - Christian Brambilla
AU - Elisabeth Brambilla
AU - Graham Byrnes
AU - Ghislaine Scelo
AU - Florence Le Calvez-Kelm
AU - Matthieu Foll
AU - James D Mckay
AU - Paul Brennan
PY - 2026
DA - 2026/10/28
JO - EBioMedicine
DO - 10.1016/j.ebiom.2016.06.032
UR - https://hal.science/hal-05842798v1
AB - 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.
SN - 2352-3964
ER -