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

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...

Full description

Saved in:
Bibliographic Details
Published in:Molecular oncology 2015-04, Vol.9 (4), p.783-790
Main Authors: Lebofsky, Ronald, Decraene, Charles, Bernard, Virginie, Kamal, Maud, Blin, Anthony, Leroy, Quentin, Rio Frio, Thomas, Pierron, Gaëlle, Callens, Céline, Bieche, Ivan, Saliou, Adrien, Madic, Jordan, Rouleau, Etienne, Bidard, François-Clément, Lantz, Olivier, Stern, Marc-Henri, Le Tourneau, Christophe, Pierga, Jean-Yves
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Biopsy
Cancer therapies
Circulating tumor DNA
Deoxyribonucleic acid
DNA
DNA, Neoplasm - blood
DNA, Neoplasm - metabolism
Feasibility studies
Female
Gene Frequency - genetics
Genes
Genotyping
Genotyping Techniques
Histology
Humans
Laboratories
Liquid biopsy
Liver
Lymphatic system
Metastases
Metastasis
Middle Aged
Multiple tumor types
Mutation
Mutation - genetics
Neoplasm Metastasis
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - pathology
Neoplastic Cells, Circulating - metabolism
Neoplastic Cells, Circulating - pathology
Next-generation sequencing
Patients
Plasma
Precision Medicine
SHIVA trial
Thyroid gland
Citations: Items that this one cites
Items that cite this one
Online Access:Request full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. •We report de novo multiplexed detection of targetable ctDNA mutations.•We report ctDNA mutations detection from multiple tumor types (SHIVA trial).•There is no correlation between ctDNA and total plasma DNA quantity.•ctDNA corresponds to ∼25% of total cfDNA fraction for detectable plasma mutations.•ctDNA is as remarkable surrogate of tumor biopsy for de novo mutation calling.
ISSN:1574-7891
1878-0261
DOI:10.1016/j.molonc.2014.12.003