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Article ; Online: Circulating tumor cells in breast cancer.

Bidard, Francois-Clement / Proudhon, Charlotte / Pierga, Jean-Yves

2016 Volume 10, Issue 3, Page(s) 418–430

Abstract: Over the past decade, technically reliable circulating tumor cell (CTC) detection methods allowed the collection of large datasets of CTC counts in cancer patients. These data can be used either as a dynamic prognostic biomarker or as tumor material for " ...

Abstract	Over the past decade, technically reliable circulating tumor cell (CTC) detection methods allowed the collection of large datasets of CTC counts in cancer patients. These data can be used either as a dynamic prognostic biomarker or as tumor material for "liquid biopsy". Breast cancer appears to be the cancer type in which CTC have been the most extensively studied so far, with level-of-evidence-1 studies supporting the clinical validity of CTC count in both early and metastatic stage. This review summarizes and discusses the clinical results obtained in breast cancer patients, the issues faced by the molecular characterization of CTC and the biological findings about cancer biology and metastasis that were obtained from CTC.
MeSH term(s)	Animals ; Biopsy/methods ; Breast Neoplasms/blood ; Breast Neoplasms/diagnosis ; Breast Neoplasms/pathology ; Female ; Humans ; Neoplasm Metastasis/diagnosis ; Neoplasm Metastasis/pathology ; Neoplastic Cells, Circulating/pathology ; Prognosis
Language	English
Publishing date	2016-01-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2415106-3
ISSN	1878-0261 ; 1574-7891
ISSN (online)	1878-0261
ISSN	1574-7891
DOI	10.1016/j.molonc.2016.01.001
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Article: Deciphering HER2-HER3 Dimerization at the Single CTC Level: A Microfluidic Approach.

Tulukcuoglu Guneri, Ezgi / Lakis, Emile / Hajji, Ismail / Martin, Elian / Champ, Jerome / Rampanou, Aurore / Pierga, Jean-Yves / Viovy, Jean-Louis / Proudhon, Charlotte / Bidard, François-Clément / Descroix, Stéphanie

Cancers

2022 Volume 14, Issue 8

Abstract: Microfluidics has provided clinicians with new technologies to detect and analyze circulating tumor biomarkers in order to further improve their understanding of disease mechanism, as well as to improve patient management. Among these different ... ...

Abstract	Microfluidics has provided clinicians with new technologies to detect and analyze circulating tumor biomarkers in order to further improve their understanding of disease mechanism, as well as to improve patient management. Among these different biomarkers, circulating tumor cells have proven to be of high interest for different types of cancer and in particular for breast cancer. Here we focus our attention on a breast cancer subtype referred as HER2-positive breast cancer, this cancer being associated with an amplification of HER2 protein at the plasma membrane of cancer cells. Combined with therapies targeting the HER2 protein, HER2-HER3 dimerization blockade further improves a patient's outcome. In this work, we propose a new approach to CTC characterization by on-chip integrating proximity ligation assay, so that we can quantify the HER2-HER3 dimerization event at the level of single CTC. To achieve this, we developed a microfluidic approach combining both CTC capture, identification and HER2-HER3 status quantification by Proximity Ligation Assay (PLA). We first optimized and demonstrated the potential of the on-chip quantification of HER2-HER3 dimerization using cancer cell lines with various levels of HER2 overexpression and validated its clinical potential with a patient's sample treated or not with HER2-targeted therapy.
Language	English
Publishing date	2022-04-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14081890
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Article ; Online: Circulating Tumor Cells in Early Breast Cancer.

Thery, Laura / Meddis, Alessandra / Cabel, Luc / Proudhon, Charlotte / Latouche, Aurelien / Pierga, Jean-Yves / Bidard, Francois-Clement

JNCI cancer spectrum

2019 Volume 3, Issue 2, Page(s) pkz026

Abstract: Circulating tumor cells (CTCs) are particularly rare in non-metastatic breast cancer, and the clinical validity of CTC detection in that clinical setting was initially not well recognized. A cytological CTC detection device (CellSearch) fulfilling the ... ...

Abstract	Circulating tumor cells (CTCs) are particularly rare in non-metastatic breast cancer, and the clinical validity of CTC detection in that clinical setting was initially not well recognized. A cytological CTC detection device (CellSearch) fulfilling the CLIA requirements for analytical validity was subsequently developed and, in 2008, we reported the first study (REMAGUS02) showing that distant metastasis-free survival was shorter in early breast cancer patients with one or more CTCs. In the past 10 years, other clinical studies and meta-analyses have established CTC detection as a level-of-evidence 1 prognostic biomarker for local relapses, distant relapses, and overall survival. This review summarizes available data on CTC detection and the promises of this proliferation- and subtype-independent metastasis-associated biomarker in early breast cancer patients.
Language	English
Publishing date	2019-04-27
Publishing country	England
Document type	Journal Article
ISSN	2515-5091
ISSN (online)	2515-5091
DOI	10.1093/jncics/pkz026
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Article ; Online: Identification and resolution of artifacts in the interpretation of imprinted gene expression.

Proudhon, Charlotte / Bourc'his, Déborah

Briefings in functional genomics

2010 Volume 9, Issue 5-6, Page(s) 374–384

Abstract: Genomic imprinting refers to genes that are epigenetically programmed in the germline to express exclusively or preferentially one allele in a parent-of-origin manner. Expression-based genome-wide screening for the identification of imprinted genes has ... ...

Abstract	Genomic imprinting refers to genes that are epigenetically programmed in the germline to express exclusively or preferentially one allele in a parent-of-origin manner. Expression-based genome-wide screening for the identification of imprinted genes has failed to uncover a significant number of new imprinted genes, probably because of the high tissue- and developmental-stage specificity of imprinted gene expression. A very large number of technical and biological artifacts can also lead to the erroneous evidence of imprinted gene expression. In this article, we focus on three common sources of potential confounding effects: (i) random monoallelic expression in monoclonal cell populations, (ii) genetically determined monoallelic expression and (iii) contamination or infiltration of embryonic tissues with maternal material. This last situation specifically applies to genes that occur as maternally expressed in the placenta. Beside the use of reciprocal crosses that are instrumental to confirm the parental specificity of expression, we provide additional methods for the detection and elimination of these situations that can be misinterpreted as cases of imprinted expression.
MeSH term(s)	Alleles ; Animals ; Artifacts ; Female ; Gene Expression ; Genetic Testing/methods ; Genome ; Genomic Imprinting ; Humans ; Mice ; Placenta/metabolism ; Pregnancy
Language	English
Publishing date	2010-09-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2540916-5
ISSN	2041-2657 ; 2041-2649 ; 2041-2647
ISSN (online)	2041-2657
ISSN	2041-2649 ; 2041-2647
DOI	10.1093/bfgp/elq020
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Article: Shallow Whole-Genome Sequencing from Plasma Identifies FGFR1 Amplified Breast Cancers and Predicts Overall Survival.

Bourrier, Chantal / Pierga, Jean-Yves / Xuereb, Laura / Salaun, Hélène / Proudhon, Charlotte / Speicher, Michael R / Belic, Jelena / Heitzer, Ellen / Lockhart, Brian Paul / Guigal-Stephan, Nolwen

Cancers

2020 Volume 12, Issue 6

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2020-06-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12061481
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Article: Evolution de l'empreinte parentale chez les mammifères: quelle ménagerie!

Proudhon, Charlotte / Bourc'his, Déborah

Medecine sciences : M/S

2010 Volume 26, Issue 5, Page(s) 497–503

Abstract: Genomic imprinting imposes an obligate mode of biparental reproduction in mammals. This phenomenon results from the monoparental expression of a subset of genes. This specific gene regulation mechanism affects viviparous mammals, especially eutherians, ... ...

Title translation	Evolution of genomic imprinting in mammals: what a zoo!.
Abstract	Genomic imprinting imposes an obligate mode of biparental reproduction in mammals. This phenomenon results from the monoparental expression of a subset of genes. This specific gene regulation mechanism affects viviparous mammals, especially eutherians, but also marsupials to a lesser extent. Oviparous mammals, or monotremes, do not seem to demonstrate monoparental allele expression. This phylogenic confinement suggests that the evolution of the placenta imposed a selective pressure for the emergence of genomic imprinting. This physiological argument is now complemented by recent genomic evidence facilitated by the sequencing of the platypus genome, a rare modern day case of a monotreme. Analysis of the platypus genome in comparison to eutherian genomes shows a chronological and functional coincidence between the appearance of genomic imprinting and transposable element accumulation. The systematic comparative analyses of genomic sequences in different species is essential for the further understanding of genomic imprinting emergence and divergent evolution along mammalian speciation.
MeSH term(s)	Animals ; Biological Evolution ; DNA Methylation ; DNA Transposable Elements ; Epigenesis, Genetic/genetics ; Female ; Gene Expression Regulation, Developmental/genetics ; Genomic Imprinting/genetics ; Humans ; Male ; Mammals/embryology ; Mammals/genetics ; Marsupialia/embryology ; Marsupialia/genetics ; Mice/embryology ; Mice/genetics ; Phylogeny ; Placenta/physiology ; Platypus/embryology ; Platypus/genetics ; Pregnancy ; Species Specificity ; Vertebrates/embryology ; Vertebrates/genetics
Chemical Substances	DNA Transposable Elements
Language	French
Publishing date	2010-05
Publishing country	France
Document type	Comparative Study ; English Abstract ; Journal Article ; Review
ZDB-ID	632733-3
ISSN	1958-5381 ; 0767-0974
ISSN (online)	1958-5381
ISSN	0767-0974
DOI	10.1051/medsci/2010265497
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Article: Sexual dimorphism in parental imprint ontogeny and contribution to embryonic development.

Bourc'his, Déborah / Proudhon, Charlotte

Molecular and cellular endocrinology

2008 Volume 282, Issue 1-2, Page(s) 87–94

Abstract: Genomic imprinting refers to the functional non-equivalence of parental genomes in mammals that results from the parent-of-origin allelic expression of a subset of genes. Parent-specific expression is dependent on the germ line acquisition of DNA ... ...

Abstract	Genomic imprinting refers to the functional non-equivalence of parental genomes in mammals that results from the parent-of-origin allelic expression of a subset of genes. Parent-specific expression is dependent on the germ line acquisition of DNA methylation marks at imprinting control regions (ICRs), coordinated by the DNA-methyltransferase homolog DNMT3L. We discuss here how the gender-specific stages of DNMT3L expression may have influenced the various sexually dimorphic aspects of genomic imprinting: (1) the differential developmental timing of methylation establishment at paternally and maternally imprinted genes in each parental germ line, (2) the differential dependence on DNMT3L of parental methylation imprint establishment, (3) the unequal duration of paternal versus maternal methylation imprints during germ cell development, (4) the biased distribution of methylation-dependent ICRs towards the maternal genome, (5) the different genomic organization of paternal versus maternal ICRs, and finally (6) the overwhelming contribution of maternal germ line imprints to development compared to their paternal counterparts.
MeSH term(s)	Animals ; DNA (Cytosine-5-)-Methyltransferases/genetics ; DNA (Cytosine-5-)-Methyltransferases/physiology ; DNA Methylation ; Embryonic Development/genetics ; Embryonic Development/physiology ; Female ; Gene Expression Regulation, Developmental/physiology ; Genomic Imprinting/genetics ; Genomic Imprinting/physiology ; Germ Cells ; Humans ; Male ; Sex Characteristics
Chemical Substances	DNMT3L protein, human (EC 2.1.1.-) ; DNA (Cytosine-5-)-Methyltransferases (EC 2.1.1.37)
Language	English
Publishing date	2008-01-30
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	187438-x
ISSN	1872-8057 ; 0303-7207
ISSN (online)	1872-8057
ISSN	0303-7207
DOI	10.1016/j.mce.2007.11.025
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Article ; Online: Clinical potential of circulating tumour DNA in patients receiving anticancer immunotherapy.

Cabel, Luc / Proudhon, Charlotte / Romano, Emanuela / Girard, Nicolas / Lantz, Olivier / Stern, Marc-Henri / Pierga, Jean-Yves / Bidard, François-Clément

Nature reviews. Clinical oncology

2018 Volume 15, Issue 10, Page(s) 639–650

Abstract: Considerable interest surrounds the use of immune-checkpoint inhibitors in patients with solid tumours following the demonstration of the impressive clinical efficacy of anti-programmed cell death protein 1 and anti-programmed cell death 1 ligand 1 ... ...

Abstract	Considerable interest surrounds the use of immune-checkpoint inhibitors in patients with solid tumours following the demonstration of the impressive clinical efficacy of anti-programmed cell death protein 1 and anti-programmed cell death 1 ligand 1 antibodies in several tumour types. However, the emergence of unexpected tumour response patterns, such as pseudoprogression or hyperprogression, might complicate the management of patients receiving these agents. Analysis of circulating tumour DNA (ctDNA) has been shown to have prognostic value by enabling the detection of residual proliferating disease in the adjuvant setting and estimation of tumour burden in the metastatic setting, which are key stratification biomarkers for use of immune-checkpoint inhibition (ICI). Furthermore, examinations of ctDNA for genetic predictors of responsiveness to immunotherapy, such as mutations, tumour mutational load, and microsatellite instability provide a noninvasive surrogate for tumour biopsy sampling. Proof-of-concept reports have also demonstrated that quantitative changes in ctDNA levels early in the course of disease are a promising tool for the assessment of responsiveness to ICI that might complement standard imaging approaches. Other applications of this technology are also currently under investigation, such as early detection of resistance to immunotherapy and characterization of mechanisms of resistance. The aim of this Review is to summarize available data on the application of ctDNA in patients receiving immunotherapy and to discuss the most promising future directions.
MeSH term(s)	B7-H1 Antigen/antagonists & inhibitors ; B7-H1 Antigen/immunology ; Biomarkers, Tumor/blood ; Circulating Tumor DNA/blood ; Humans ; Immunotherapy ; Mutation ; Neoplasms/blood ; Neoplasms/pathology ; Neoplasms/therapy
Chemical Substances	B7-H1 Antigen ; Biomarkers, Tumor ; CD274 protein, human ; Circulating Tumor DNA
Language	English
Publishing date	2018-07-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2491410-1
ISSN	1759-4782 ; 1759-4774
ISSN (online)	1759-4782
ISSN	1759-4774
DOI	10.1038/s41571-018-0074-3
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Article ; Online: Single Droplet Digital Polymerase Chain Reaction for Comprehensive and Simultaneous Detection of Mutations in Hotspot Regions.

Decraene, Charles / Bortolini Silveira, Amanda / Michel, Marc / Bidard, François-Clément / Pierga, Jean-Yves / Stern, Marc-Henri / Proudhon, Charlotte

Journal of visualized experiments : JoVE

2018 , Issue 139

Abstract: Droplet digital polymerase chain reaction (ddPCR) is a highly sensitive quantitative polymerase chain reaction (PCR) method based on sample fractionation into thousands of nano-sized water-in-oil individual reactions. Recently, ddPCR has become one of ... ...

Abstract	Droplet digital polymerase chain reaction (ddPCR) is a highly sensitive quantitative polymerase chain reaction (PCR) method based on sample fractionation into thousands of nano-sized water-in-oil individual reactions. Recently, ddPCR has become one of the most accurate and sensitive tools for circulating tumor DNA (ctDNA) detection. One of the major limitations of the standard ddPCR technique is the restricted number of mutations that can be screened per reaction, as specific hydrolysis probes recognizing each possible allelic version are required. An alternative methodology, the drop-off ddPCR, increases throughput, since it requires only a single pair of probes to detect and quantify potentially all genetic alterations in the targeted region. Drop-off ddPCR displays comparable sensitivity to conventional ddPCR assays with the advantage of detecting a greater number of mutations in a single reaction. It is cost-effective, conserves precious sample material, and can also be used as a discovery tool when mutations are not known a priori.
MeSH term(s)	Circulating Tumor DNA/metabolism ; Humans ; Mutation ; Polymerase Chain Reaction/methods
Chemical Substances	Circulating Tumor DNA
Language	English
Publishing date	2018-09-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/58051
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Article ; Online: High-Accuracy Determination of Microsatellite Instability Compatible with Liquid Biopsies.

Silveira, Amanda Bortolini / Bidard, François-Clément / Kasperek, Amélie / Melaabi, Samia / Tanguy, Marie-Laure / Rodrigues, Manuel / Bataillon, Guillaume / Cabel, Luc / Buecher, Bruno / Pierga, Jean-Yves / Proudhon, Charlotte / Stern, Marc-Henri

Clinical chemistry

2020 Volume 66, Issue 4, Page(s) 606–613

Abstract: Background: Microsatellite instability (MSI) has recently emerged as a predictive pan-tumor biomarker of immunotherapy efficacy, stimulating the development of diagnostic tools compatible with large-scale screening of patients. In this context, ... ...

Abstract	Background: Microsatellite instability (MSI) has recently emerged as a predictive pan-tumor biomarker of immunotherapy efficacy, stimulating the development of diagnostic tools compatible with large-scale screening of patients. In this context, noninvasive detection of MSI from circulating tumor DNA stands as a promising diagnostic and posttreatment monitoring tool. Methods: We developed drop-off droplet-digital PCR (ddPCR) assays targeting BAT-26, activin A receptor type 2A (ACVR2A), and defensin beta 105A/B (DEFB105A/B) microsatellite markers. Performances of the assays were measured on reconstitution experiments of various mutant allelic fractions, on 185 tumor samples with known MSI status, and on 72 blood samples collected from 42 patients with advanced colorectal or endometrial cancers before and/or during therapy. Results: The 3 ddPCR assays reached analytical sensitivity <0.1% variant allelic frequency and could reliably detect and quantify MSI in both tumor and body fluid samples. High concordance between MSI status determination by the three-marker ddPCR test and the reference pentaplex method were observed (100% for colorectal tumors and 93% for other tumor types). Moreover, the 3 assays showed correlations with r ≥ 0.99 with other circulating tumor DNA markers and their dynamic during treatment correlated well with clinical response. Conclusions: This innovative approach for MSI detection provides a noninvasive, cost-effective, and fast diagnostic tool, well suited for large-scale screening of patients that may benefit from immunotherapy agents, as well as for monitoring treatment responses.
MeSH term(s)	Activin Receptors, Type II/genetics ; Biomarkers, Tumor ; Cell Line, Tumor ; Circulating Tumor DNA/blood ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Endometrial Neoplasms/drug therapy ; Endometrial Neoplasms/genetics ; Endometrial Neoplasms/pathology ; False Positive Reactions ; Female ; Genetic Markers ; Humans ; Limit of Detection ; Liquid Biopsy ; Microsatellite Instability ; Microsatellite Repeats ; Polymerase Chain Reaction/methods ; beta-Defensins/genetics
Chemical Substances	BAT26 microsatellite DNA ; Biomarkers, Tumor ; Circulating Tumor DNA ; DEFB105A protein, human ; Genetic Markers ; beta-Defensins ; Activin Receptors, Type II (EC 2.7.11.30) ; activin receptor type II-A (EC 2.7.11.30)
Language	English
Publishing date	2020-03-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80102-1
ISSN	1530-8561 ; 0009-9147
ISSN (online)	1530-8561
ISSN	0009-9147
DOI	10.1093/clinchem/hvaa013
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