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Journal articles
Genetic characterization of a unique neuroendocrine transdifferentiation prostate circulating tumor cell-derived eXplant model
Vincent Faugeroux
1, 2
Emma Pailler
1, 2
Marianne Oulhen
2
Olivier Déas
3
Laura Brulle-Soumare
3
Céline Hervieu
1, 2
Virginie Marty
4
Kamelia Alexandrova
5
Kiki Andree
6
Nikolas Stoecklein
7
Dominique Tramalloni
5
Stefano Cairo
3
Maud Ngocamus
8
Claudio Nicotra
8
Leon Terstappen
6
Nicolo Manaresi
9
Valérie Lapierre
5
Karim Fizazi
1, 8
Jean-Yves Scoazec
4
Yohann Loriot
8, *
Jean-Gabriel Judde
3
Françoise Farace
1, 2, *
*
Corresponding author
1
U981 - Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse
2
Plateforme Cellules Circulantes Rares
AMMICa - Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse
Vincent Faugeroux 1, 2
Author
Emma Pailler 1, 2
Author
Marianne Oulhen 2
Author
Olivier Déas 3
Author
Laura Brulle-Soumare 3
Author
Céline Hervieu 1, 2
Author
Virginie Marty 4
Author
Kamelia Alexandrova 5
Author
Kiki C Andree 6
Author
Nikolas H Stoecklein 7
Author
Dominique Tramalloni 5
Author
Stefano Cairo 3
Author
Maud Ngocamus 8
Author
Claudio Nicotra 8
Author
Leon W M M Terstappen 6
Author
Nicolo Manaresi 9
Author
Valérie Lapierre 5
Author
Karim Fizazi 1, 8
Author
Jean-Yves Scoazec 4
Author
Yohann Loriot 8
Correspondent author
Jean-Gabriel Judde 3
Author
Françoise Farace 1, 2
Correspondent author
1
U981 - Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (Gustave Roussy.
Bâtiment de médecine moléculaire,
114, rue Édouard-Vaillant
94805 Villejuif Cedex -France - France)
- UP11 - Université Paris-Sud - Paris 11 (Bâtiment 300 - 91405 Orsay cedex - France)
- IGR - Institut Gustave Roussy (114, rue Édouard-Vaillant 94805 Villejuif Cedex -France - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U981 (101, rue de Tolbiac, 75013 Paris - France)
2
Plateforme Cellules Circulantes Rares (France)
- AMMICa - Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (Gustave-Roussy
114, rue Édouard Vaillant
94805 Villejuif - France)
- UP11 - Université Paris-Sud - Paris 11 (Bâtiment 300 - 91405 Orsay cedex - France)
- IGR - Institut Gustave Roussy (114, rue Édouard-Vaillant 94805 Villejuif Cedex -France - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : US23 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMS3655 (France)
3
XenTech [Évry] (France)
4
AMMICa - Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (Gustave-Roussy
114, rue Édouard Vaillant
94805 Villejuif - France)
- UP11 - Université Paris-Sud - Paris 11 (Bâtiment 300 - 91405 Orsay cedex - France)
- IGR - Institut Gustave Roussy (114, rue Édouard-Vaillant 94805 Villejuif Cedex -France - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : US23 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMS3655 (France)
5
Department of Cell Therapy [Villejuif] (France)
- IGR - Institut Gustave Roussy (114, rue Édouard-Vaillant 94805 Villejuif Cedex -France - France)
- Université Paris-Saclay (Espace Technologique, Bat. Discovery - RD 128 - 2e ét., 91190 Saint-Aubin - France)
6
University of Twente [Netherlands] (Drienerlolaan 5, 7522 NB Enschede - Netherlands)
7
Heinrich-Heine-Universität Düsseldorf [Düsseldorf] (Universitätsstr. 1
40225 Düsseldorf - Germany)
8
Département de médecine oncologique [Gustave Roussy] (Gustave Roussy. 114, rue Édouard-Vaillant 94805 Villejuif Cedex -France - France)
- IGR - Institut Gustave Roussy (114, rue Édouard-Vaillant 94805 Villejuif Cedex -France - France)
Abstract : Transformation of castration-resistant prostate cancer (CRPC) into an aggressive neuroendocrine disease (CRPC-NE) represents a major clinical challenge and experimental models are lacking. A CTC-derived eXplant (CDX) and a CDX-derived cell line are established using circulating tumor cells (CTCs) obtained by diagnostic leukapheresis from a CRPC patient resistant to enzalutamide. The CDX and the derived-cell line conserve 16% of primary tumor (PT) and 56% of CTC mutations, as well as 83% of PT copy-number aberrations including clonal TMPRSS2-ERG fusion and NKX3.1 loss. Both harbor an androgen receptor-null neuroendocrine phenotype, TP53, PTEN and RB1 loss. While PTEN and RB1 loss are acquired in CTCs, evolutionary analysis suggest that a PT subclone harboring TP53 loss is the driver of the metastatic event leading to the CDX. This CDX model provides insights on the sequential acquisition of key drivers of neuroendocrine transdifferentiation and offers a unique tool for effective drug screening in CRPC-NE management.
Document type :
Journal articles
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https://www.hal.inserm.fr/inserm-02735341
Contributor : Myriam Bodescot <>
Submitted on : Tuesday, June 2, 2020 - 3:47:19 PM
Last modification on : Monday, December 14, 2020 - 5:38:16 PM
Long-term archiving on: : Wednesday, December 2, 2020 - 3:02:33 PM
Contributor : Myriam Bodescot <>
Submitted on : Tuesday, June 2, 2020 - 3:47:19 PM
Last modification on : Monday, December 14, 2020 - 5:38:16 PM
Long-term archiving on: : Wednesday, December 2, 2020 - 3:02:33 PM
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s41467-020-15426-2.pdf
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Identifiers
- HAL Id : inserm-02735341, version 1
- DOI : 10.1038/s41467-020-15426-2
- PUBMED : 32313004
- PUBMEDCENTRAL : PMC7171138
Collections
FNCLCC | CNRS | SORBONNE-UNIVERSITE | IGR | SU-TI
Citation
Vincent Faugeroux, Emma Pailler, Marianne Oulhen, Olivier Déas, Laura Brulle-Soumare, et al.. Genetic characterization of a unique neuroendocrine transdifferentiation prostate circulating tumor cell-derived eXplant model. Nature Communications, Nature Publishing Group, 2020, 11 (1), pp.1884. ⟨10.1038/s41467-020-15426-2⟩. ⟨inserm-02735341⟩
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