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Clin Cancer Res. 2014 Sep 1;20(17):4613-24. doi: 10.1158/1078-0432.CCR-13-3063. Epub 2014 Jul 10.

Noninvasive diagnosis of actionable mutations by deep sequencing of circulating free DNA in lung cancer from never-smokers: a proof-of-concept study from BioCAST/IFCT-1002.

Author information

1
International Agency for Research on Cancer, Section of Mechanisms of Carcinogenesis, Molecular Mechanisms and Biomarkers Group, Lyon Cedex, France. Department of Pulmonology, Lyon Sud University Hospital, Hospices Civils de Lyon, Lyon, France. Lyon Sud Faculty of Medicine, Lyon 1 University, Pierre Bénite Cedex, France. sebastien.couraud@chu-lyon.fr.
2
International Agency for Research on Cancer, Section of Mechanisms of Carcinogenesis, Molecular Mechanisms and Biomarkers Group, Lyon Cedex, France. Laboratorio de Genómica, Instituto Nacional de Cancerología, Tlalpan, México. Unidad de Biomedicina, FES-Iztacala, UNAM, México.
3
International Agency for Research on Cancer, Section of Mechanisms of Carcinogenesis, Molecular Mechanisms and Biomarkers Group, Lyon Cedex, France.
4
International Agency for Research on Cancer, Genetic Cancer Susceptibility Group, Lyon Cedex, France.
5
Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada. Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada.
6
The Jean Dausset Foundation - CEPH, Paris, France.
7
Department of Respiratory Medicine, Hôpital Louis Pradel, Hospices Civils de Lyon, Lyon, France. Claude Bernard University Lyon 1, Lyon (Bron), France.
8
Department of Pulmonology, Paris - Saint Joseph Hospital, and Sorbonne Paris Cité university, France.
9
Pulmonology Unit, University Hospital of Tours, France and François Rabelais University, Respiratory Diseases Study Centre, Tours, France.
10
Francois Baclesse Cancer Institute, Caen, France.
11
Department of Chest, Strasbourg University Hospital, Strasbourg, France.
12
Department of Pulmonology, Saint Joseph-Saint Luc Hospital, Lyon, France.
13
Department of Respiratory Department, Percy Military Hospital, Clamart, France.
14
Department of Pulmonology, Mâcon Hospital, Mâcon, France.
15
Thoracic Oncology, Dijon University Hospital, Dijon, France.
16
Department of Oncology, Montélimar Hospital, Montélimar, France.
17
Intergroupe Francophone de Cancérologie Thoracique, Paris, France.
18
Pulmonology and Thoracic Oncology Unit and UMR 1086 Inserm "Cancers and Préventions," Caen University Hospital, Caen, France.
19
Department of Pulmonology, Lyon Sud University Hospital, Hospices Civils de Lyon, Lyon, France. Lyon Sud Faculty of Medicine, Lyon 1 University, Pierre Bénite Cedex, France.

Abstract

PURPOSE:

Tumor somatic mutation analysis is part of the standard management of metastatic lung cancer. However, physicians often have to deal with small biopsies and consequently with challenging mutation testing. Circulating free DNA (cfDNA) is a promising tool for accessing the tumor genome as a liquid biopsy. Here, we evaluated next-generation sequencing (NGS) on cfDNA samples obtained from a consecutive series of patients for the screening of a range of clinically relevant mutations.

EXPERIMENTAL DESIGN:

A total of 107 plasma samples were collected from the BioCAST/IFCT-1002 lung cancer study (never-smokers cohort). Matched tumor DNA (tDNA) was obtained for 68 cases. Multiplex PCR-based assays were designed to target specific coding regions in EGFR, KRAS, BRAF, ERBB2, and PI3KCA genes, and amplicon sequencing was performed at deep coverage on the cfDNA/tDNA pairs using the NGS IonTorrent Personal Genome Machine Platform.

RESULTS:

CfDNA concentration in plasma was significantly associated with both stage and number of metastatic sites. In tDNA, 50 mutations (36 EGFR, 5 ERBB2, 4 KRAS, 3 BRAF, and 2 PIK3CA) were identified, of which 26 were detected in cfDNA. Sensitivity of the test was 58% (95% confidence interval, 43%-71%) and the estimated specificity was 87% (62%-96%).

CONCLUSION:

These data demonstrate the feasibility and potential utility of mutation screening in cfDNA using IonTorrent NGS for the detection of a range of tumor biomarkers in patients with metastatic lung cancer.

PMID:
25013125
DOI:
10.1158/1078-0432.CCR-13-3063
[Indexed for MEDLINE]
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