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 op...

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Published in:EBioMedicine Vol. 10; no. C; pp. 117 - 123
Main Authors: Fernandez-Cuesta, Lynnette, Perdomo, Sandra, Avogbe, Patrice H., 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, Brambilla, Elisabeth, Byrnes, Graham, Scelo, Ghislaine, Le Calvez-Kelm, Florence, Foll, Matthieu, McKay, James D., Brennan, Paul
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01.08.2016
Elsevier
Subjects:
Advanced Basic Science
Biomarkers, Tumor
Case-Control Studies
cfDNA
ctDNA
DNA, Neoplasm - blood
Early detection
Early Detection of Cancer
Female
Humans
Internal Medicine
Leukocytes - metabolism
Lung Neoplasms - blood
Lung Neoplasms - diagnosis
Lung Neoplasms - genetics
Male
Mutation
Neoplasm Staging
Research Paper
Screening
Small Cell Lung Carcinoma - blood
Small Cell Lung Carcinoma - diagnosis
Small Cell Lung Carcinoma - genetics
Small-cell lung cancer
TP53 mutations
Tumor Suppressor Protein p53 - genetics
Screening
TP53 mutations
Small-cell lung cancer
cfDNA
ctDNA
Early detection
ISSN:2352-3964, 2352-3964
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Summary: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. •CtDNA may play a crucial role in the detection of pre-clinical cancer.•TP53 mutations are detectable in the cfDNA of SCLC patients with early-stage tumors.•Detection of TP53 mutations in non-cancer controls poses serious challenges for the development of ctDNA screening tests. Cell-free DNA (cfDNA) has potential for monitoring response to treatment and relapse, but also for early detection. This is the first study reporting the detection of circulating-tumor DNA (ctDNA) in cases diagnosed with small-cell lung cancer (SCLC). Our results show that TP53 mutations are detectable in the cfDNA of SCLC patients including those with early-stage tumors. Importantly, we also provide evidence that cancer-like TP53 mutations are present in non-cancer controls, which poses serious challenges for the development of ctDNA screening tests.
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ISSN:2352-3964
2352-3964
DOI:10.1016/j.ebiom.2016.06.032