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EBioMedicine. 2016 Aug;10:117-23. doi: 10.1016/j.ebiom.2016.06.032. Epub 2016 Jun 25.

Identification of Circulating Tumor DNA for the Early Detection of Small-cell Lung Cancer.

Author information

1
International Agency for Research on Cancer (IARC-WHO), 150 cours Albert Thomas, 69008 Lyons, France.
2
International Agency for Research on Cancer (IARC-WHO), 150 cours Albert Thomas, 69008 Lyons, France; Institute of Nutrition, Genetics and Metabolism Research, Universidad El Bosque, Bogot√°, Colombia.
3
Russian N.N. Blokhin Cancer Research Centre, Moscow, Russian Federation.
4
Instituto Angel Roffo, Buenos Aires, Argentina.
5
1st Faculty of Medicine, Charles University, Prague, Czech Republic.
6
CRO Aviano National Cancer Institute, Aviano, Italy.
7
Department of Molecular Medicine, University of Padova, Padova, Italy.
8
University of Athens Medical School, Greece.
9
CHU Grenoble, University Grenoble- Alpes, INSERM U823, Grenoble, France.
10
International Agency for Research on Cancer (IARC-WHO), 150 cours Albert Thomas, 69008 Lyons, France. Electronic address: MckayJ@iarc.fr.
11
International Agency for Research on Cancer (IARC-WHO), 150 cours Albert Thomas, 69008 Lyons, France. Electronic address: BrennanP@iarc.fr.

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.

KEYWORDS:

Early detection; Screening; Small-cell lung cancer; TP53 mutations; cfDNA; ctDNA

PMID:
27377626
PMCID:
PMC5036515
DOI:
10.1016/j.ebiom.2016.06.032
[Indexed for MEDLINE]
Free PMC Article

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