BRCAness, SLFN11, and RB1 loss predict response to topoisomerase I inhibitors in triple-negative breast cancers

Florence Coussy; Rania El-Botty; Sophie Château-Joubert; Ahmed Dahmani; Elodie Montaudon; Sophie Leboucher; Ludivine Morisset; Pierre Painsec; Laura Sourd; Léa Huguet; Fariba Nemati; Jean-Luc Servely; Thibaut Larcher; Sophie Vacher; Adrien Briaux; Cécile Reyes; Philippe La Rosa; Georges Lucotte; Tatiana Popova; Pierre Foidart; Nor Eddine Sounni; Agnès Noel; Didier Decaudin; Laetitia Fuhrmann; Anne Salomon; Fabien Reyal; Christopher Mueller; Petra Ter Brugge; Jos Jonkers; Marie-France Poupon; Marc-Henri Stern; Ivan Bièche; Yves Pommier; Elisabetta Marangoni

doi:10.1126/scitranslmed.aax2625

Research ArticleCancer

BRCAness, SLFN11, and RB1 loss predict response to topoisomerase I inhibitors in triple-negative breast cancers

View ORCID ProfileFlorence Coussy¹,²,³,
View ORCID ProfileRania El-Botty¹,
Sophie Château-Joubert⁴,
Ahmed Dahmani¹,
Elodie Montaudon¹,
View ORCID ProfileSophie Leboucher⁵,
Ludivine Morisset¹,
Pierre Painsec¹,
Laura Sourd¹,
Léa Huguet¹,
Fariba Nemati¹,
Jean-Luc Servely⁴,⁶,
View ORCID ProfileThibaut Larcher⁷,
View ORCID ProfileSophie Vacher³,
Adrien Briaux³,
Cécile Reyes¹,
Philippe La Rosa⁸,⁹,
Georges Lucotte⁸,⁹,
Tatiana Popova⁹,¹⁰,
View ORCID ProfilePierre Foidart¹¹,
Nor Eddine Sounni¹¹,
Agnès Noel¹¹,
Didier Decaudin¹,²,
View ORCID ProfileLaetitia Fuhrmann¹²,
Anne Salomon¹²,
Fabien Reyal¹³,¹⁴,
View ORCID ProfileChristopher Mueller¹⁵,
Petra Ter Brugge¹⁶,
View ORCID ProfileJos Jonkers¹⁶,
Marie-France Poupon¹,
View ORCID ProfileMarc-Henri Stern⁹,¹⁰,
Ivan Bièche³,
View ORCID ProfileYves Pommier¹⁷,* and
View ORCID ProfileElisabetta Marangoni¹,*

¹Translational Research Department, Institut Curie, PSL Research University, 75005 Paris, France.
²Medical Oncology Department, Institut Curie, PSL Research University, 75005 Paris, France.
³Genetics Department, Institut Curie, PSL Research University, 75005 Paris, France.
⁴BioPôle Alfort, Ecole Nationale Vétérinaire d'Alfort, 94704 Maisons Alfort, France.
⁵Institut Curie, PSL Research University, UMR3306, 91405 Orsay, France.
⁶INRA, PHASE Department, 37380 Nouzilly, France.
⁷INRA, APEX-PAnTher, Oniris, 44300 Nantes, France.
⁸INSERM, U900, 75005 Paris, France.
⁹Institut Curie, PSL Research University, 75005 Paris, France.
¹⁰INSERM U830, 75005 Paris, France.
¹¹Laboratory of Tumor and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliqué-Cancer (GIGA-Cancer), University of Liège, Liège 4000, Belgium.
¹²Department of Pathology, Institut Curie, PSL Research University, 75005 Paris, France.
¹³Surgery Department, Institut Curie, PSL Research University, 75005 Paris, France.
¹⁴U932, Immunity and Cancer, INSERM, Institut Curie, 75005 Paris, France.
¹⁵Queen's Cancer Research Institute, Queen's University, Kingston, ON K7L 3N6, Canada.
¹⁶Division of Molecular Pathology and Cancer Genomics Centre Netherlands, Netherlands Cancer Institute, Amsterdam, 1066 CX, Netherlands.
¹⁷Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

↵*Corresponding author. Email: elisabetta.marangoni{at}curie.fr (E.M.); pommier{at}nih.gov (Y.P.)

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Science Translational Medicine 19 Feb 2020:
Vol. 12, Issue 531, eaax2625
DOI: 10.1126/scitranslmed.aax2625

Florence Coussy

1Translational Research Department, Institut Curie, PSL Research University, 75005 Paris, France.

2Medical Oncology Department, Institut Curie, PSL Research University, 75005 Paris, France.

3Genetics Department, Institut Curie, PSL Research University, 75005 Paris, France.

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Rania El-Botty

1Translational Research Department, Institut Curie, PSL Research University, 75005 Paris, France.

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ORCID record for Rania El-Botty

Sophie Château-Joubert

4BioPôle Alfort, Ecole Nationale Vétérinaire d'Alfort, 94704 Maisons Alfort, France.

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Ahmed Dahmani

1Translational Research Department, Institut Curie, PSL Research University, 75005 Paris, France.

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Elodie Montaudon

1Translational Research Department, Institut Curie, PSL Research University, 75005 Paris, France.

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Sophie Leboucher

5Institut Curie, PSL Research University, UMR3306, 91405 Orsay, France.

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Ludivine Morisset

1Translational Research Department, Institut Curie, PSL Research University, 75005 Paris, France.

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Pierre Painsec

1Translational Research Department, Institut Curie, PSL Research University, 75005 Paris, France.

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Laura Sourd

1Translational Research Department, Institut Curie, PSL Research University, 75005 Paris, France.

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Léa Huguet

1Translational Research Department, Institut Curie, PSL Research University, 75005 Paris, France.

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Fariba Nemati

1Translational Research Department, Institut Curie, PSL Research University, 75005 Paris, France.

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Jean-Luc Servely

4BioPôle Alfort, Ecole Nationale Vétérinaire d'Alfort, 94704 Maisons Alfort, France.

6INRA, PHASE Department, 37380 Nouzilly, France.

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Thibaut Larcher

7INRA, APEX-PAnTher, Oniris, 44300 Nantes, France.

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Sophie Vacher

3Genetics Department, Institut Curie, PSL Research University, 75005 Paris, France.

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Adrien Briaux

3Genetics Department, Institut Curie, PSL Research University, 75005 Paris, France.

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Cécile Reyes

1Translational Research Department, Institut Curie, PSL Research University, 75005 Paris, France.

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Philippe La Rosa

8INSERM, U900, 75005 Paris, France.

9Institut Curie, PSL Research University, 75005 Paris, France.

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Georges Lucotte

8INSERM, U900, 75005 Paris, France.

9Institut Curie, PSL Research University, 75005 Paris, France.

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Tatiana Popova

9Institut Curie, PSL Research University, 75005 Paris, France.

10INSERM U830, 75005 Paris, France.

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Pierre Foidart

11Laboratory of Tumor and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliqué-Cancer (GIGA-Cancer), University of Liège, Liège 4000, Belgium.

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Nor Eddine Sounni

11Laboratory of Tumor and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliqué-Cancer (GIGA-Cancer), University of Liège, Liège 4000, Belgium.

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Agnès Noel

11Laboratory of Tumor and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliqué-Cancer (GIGA-Cancer), University of Liège, Liège 4000, Belgium.

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Didier Decaudin

1Translational Research Department, Institut Curie, PSL Research University, 75005 Paris, France.

2Medical Oncology Department, Institut Curie, PSL Research University, 75005 Paris, France.

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Laetitia Fuhrmann

12Department of Pathology, Institut Curie, PSL Research University, 75005 Paris, France.

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Anne Salomon

12Department of Pathology, Institut Curie, PSL Research University, 75005 Paris, France.

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Fabien Reyal

13Surgery Department, Institut Curie, PSL Research University, 75005 Paris, France.

14U932, Immunity and Cancer, INSERM, Institut Curie, 75005 Paris, France.

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Christopher Mueller

15Queen's Cancer Research Institute, Queen's University, Kingston, ON K7L 3N6, Canada.

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Petra Ter Brugge

16Division of Molecular Pathology and Cancer Genomics Centre Netherlands, Netherlands Cancer Institute, Amsterdam, 1066 CX, Netherlands.

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Jos Jonkers

16Division of Molecular Pathology and Cancer Genomics Centre Netherlands, Netherlands Cancer Institute, Amsterdam, 1066 CX, Netherlands.

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Marie-France Poupon

1Translational Research Department, Institut Curie, PSL Research University, 75005 Paris, France.

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Marc-Henri Stern

9Institut Curie, PSL Research University, 75005 Paris, France.

10INSERM U830, 75005 Paris, France.

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Ivan Bièche

3Genetics Department, Institut Curie, PSL Research University, 75005 Paris, France.

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Yves Pommier

17Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

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For correspondence: elisabetta.marangoni@curie.fr pommier@nih.gov

Elisabetta Marangoni

1Translational Research Department, Institut Curie, PSL Research University, 75005 Paris, France.

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For correspondence: elisabetta.marangoni@curie.fr pommier@nih.gov

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BRCAness, SLFN11, and RB1 loss predict response to topoisomerase I inhibitors in triple-negative breast cancers

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