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Mol Oncol. 2015 Apr;9(4):783-90. doi: 10.1016/j.molonc.2014.12.003. Epub 2014 Dec 26.

Circulating tumor DNA as a non-invasive substitute to metastasis biopsy for tumor genotyping and personalized medicine in a prospective trial across all tumor types.

Author information

1
Circulating Cancer Biomarkers Lab, SiRIC, Translational Research Department, Institut Curie, Paris, France.
2
Circulating Cancer Biomarkers Lab, SiRIC, Translational Research Department, Institut Curie, Paris, France; CNRS UMR144, Institut Curie, Paris, France.
3
ICGex NGS Platform, Institut Curie, Paris, France.
4
Department of Medical Oncology, Institut Curie, Paris and Saint-Cloud, France.
5
Oncogenetic Laboratory, Institut Curie, Paris, France.
6
Circulating Cancer Biomarkers Lab, SiRIC, Translational Research Department, Institut Curie, Paris, France; Department of Medical Oncology, Institut Curie, Paris and Saint-Cloud, France.
7
INSERM U932, Institut Curie, Paris, France; CIC-BT-507, Institut Curie, Paris, France.
8
INSERM U830, Institut Curie, Paris, France.
9
Department of Medical Oncology, Institut Curie, Paris and Saint-Cloud, France; INSERM U900, Institut Curie, Paris, France.
10
Circulating Cancer Biomarkers Lab, SiRIC, Translational Research Department, Institut Curie, Paris, France; Department of Medical Oncology, Institut Curie, Paris and Saint-Cloud, France; University Paris Descartes, Paris, France. Electronic address: jean-yves.pierga@curie.fr.

Abstract

Cell-free tumor DNA (ctDNA) has the potential to enable non-invasive diagnostic tests for personalized medicine in providing similar molecular information as that derived from invasive tumor biopsies. The histology-independent phase II SHIVA trial matches patients with targeted therapeutics based on previous screening of multiple somatic mutations using metastatic biopsies. To evaluate the utility of ctDNA in this trial, as an ancillary study we performed de novo detection of somatic mutations using plasma DNA compared to metastasis biopsies in 34 patients covering 18 different tumor types, scanning 46 genes and more than 6800 COSMIC mutations with a multiplexed next-generation sequencing panel. In 27 patients, 28 of 29 mutations identified in metastasis biopsies (97%) were detected in matched ctDNA. Among these 27 patients, one additional mutation was found in ctDNA only. In the seven other patients, mutation detection from metastasis biopsy failed due to inadequate biopsy material, but was successful in all plasma DNA samples providing three more potential actionable mutations. These results suggest that ctDNA analysis is a potential alternative and/or replacement to analyses using costly, harmful and lengthy tissue biopsies of metastasis, irrespective of cancer type and metastatic site, for multiplexed mutation detection in selecting personalized therapies based on the patient's tumor genetic content.

KEYWORDS:

Circulating tumor DNA; Liquid biopsy; Multiple tumor types; Next-generation sequencing; SHIVA trial

PMID:
25579085
PMCID:
PMC5528781
DOI:
10.1016/j.molonc.2014.12.003
[Indexed for MEDLINE]
Free PMC Article

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