Titre |
Identification of Circulating Tumor DNA for the Early Detection of Small-cell Lung Cancer |
Auteurs |
Fernandez-Cuesta Lynnette [1],
Perdomo Sandra [1],
Avogbe Hodonou Patrice [1],
Leblay Noemie [4],
Delhomme Tiffany [5],
Gaborieau Valerie [6],
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Journal: |
EBioMedicine |
Catégorie Journal: |
Internationale |
Impact factor: |
1.96 |
Volume Journal: |
10 |
DOI: |
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Resume |
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 dis- plays 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 muta- tions 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 pa- tients. 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. |
Mots clés |
ctDNA, cfDNA, Small-cell lung cancer TP53 mutations
Early detection Screening |
Pages |
117 - 123 |
Fichier |
(PDF) |