Homologous recombination deficiency derived from whole-genome sequencing predicts platinum response in triple-negative breast cancers.

Autor: Ter Brugge P; Division of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, Netherlands., Moser SC; Division of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, Netherlands., Bièche I; Genetics Department, Institut Curie, PSL University, 26 Rue d'Ulm, 75005, Paris, France., Kristel P; Division of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, Netherlands., Ibadioune S; Genetics Department, Institut Curie, PSL University, 26 Rue d'Ulm, 75005, Paris, France., Eeckhoutte A; INSERM U830, Institut Curie, PSL University, 75005, Paris, France.; Institut Curie, PSL University, 26 Rue d'Ulm, 75005, Paris, France., de Bruijn R; Division of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, Netherlands., van der Burg E; Division of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, Netherlands., Lutz C; Division of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, Netherlands., Annunziato S; Division of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, Netherlands., de Ruiter J; Division of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, Netherlands., Masliah Planchon J; Genetics Department, Institut Curie, PSL University, 26 Rue d'Ulm, 75005, Paris, France., Vacher S; Genetics Department, Institut Curie, PSL University, 26 Rue d'Ulm, 75005, Paris, France., Courtois L; Genetics Department, Institut Curie, PSL University, 26 Rue d'Ulm, 75005, Paris, France., El-Botty R; Laboratory of Preclinical Investigation, Translational Research Department, Institut Curie, PSL University, 26 Rue d'Ulm, 75005, Paris, France., Dahmani A; Laboratory of Preclinical Investigation, Translational Research Department, Institut Curie, PSL University, 26 Rue d'Ulm, 75005, Paris, France., Montaudon E; Laboratory of Preclinical Investigation, Translational Research Department, Institut Curie, PSL University, 26 Rue d'Ulm, 75005, Paris, France., Morisset L; Laboratory of Preclinical Investigation, Translational Research Department, Institut Curie, PSL University, 26 Rue d'Ulm, 75005, Paris, France., Sourd L; Laboratory of Preclinical Investigation, Translational Research Department, Institut Curie, PSL University, 26 Rue d'Ulm, 75005, Paris, France., Huguet L; Laboratory of Preclinical Investigation, Translational Research Department, Institut Curie, PSL University, 26 Rue d'Ulm, 75005, Paris, France., Derrien H; Laboratory of Preclinical Investigation, Translational Research Department, Institut Curie, PSL University, 26 Rue d'Ulm, 75005, Paris, France., Nemati F; Laboratory of Preclinical Investigation, Translational Research Department, Institut Curie, PSL University, 26 Rue d'Ulm, 75005, Paris, France., Chateau-Joubert S; BioPôle Alfort, Ecole Nationale Vétérinaire d'Alfort, 94704, Maisons Alfort, France., Larcher T; INRA, APEX-PAnTher, Oniris, 44300, Nantes, France., Salomon A; Department of Pathology, Institut Curie, PSL University, 75005, Paris, France., Decaudin D; Laboratory of Preclinical Investigation, Translational Research Department, Institut Curie, PSL University, 26 Rue d'Ulm, 75005, Paris, France., Reyal F; Department of Surgery, Institut Curie, PSL University, 75005, Paris, France., Coussy F; Department of Medical Oncology, Institut Curie, PSL University, 75005, Paris, France., Popova T; INSERM U830, Institut Curie, PSL University, 75005, Paris, France.; Institut Curie, PSL University, 26 Rue d'Ulm, 75005, Paris, France., Wesseling J; Division of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, Netherlands., Stern MH; Genetics Department, Institut Curie, PSL University, 26 Rue d'Ulm, 75005, Paris, France.; INSERM U830, Institut Curie, PSL University, 75005, Paris, France.; Institut Curie, PSL University, 26 Rue d'Ulm, 75005, Paris, France., Jonkers J; Division of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, Netherlands. j.jonkers@nki.nl., Marangoni E; Laboratory of Preclinical Investigation, Translational Research Department, Institut Curie, PSL University, 26 Rue d'Ulm, 75005, Paris, France. Elisabetta.marangoni@curie.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Apr 07; Vol. 14 (1), pp. 1958. Date of Electronic Publication: 2023 Apr 07.
DOI: 10.1038/s41467-023-37537-2
Abstrakt: The high frequency of homologous recombination deficiency (HRD) is the main rationale of testing platinum-based chemotherapy in triple-negative breast cancer (TNBC), however, the existing methods to identify HRD are controversial and there is a medical need for predictive biomarkers. We assess the in vivo response to platinum agents in 55 patient-derived xenografts (PDX) of TNBC to identify determinants of response. The HRD status, determined from whole genome sequencing, is highly predictive of platinum response. BRCA1 promoter methylation is not associated with response, in part due to residual BRCA1 gene expression and homologous recombination proficiency in different tumours showing mono-allelic methylation. Finally, in 2 cisplatin sensitive tumours we identify mutations in XRCC3 and ORC1 genes that are functionally validated in vitro. In conclusion, our results demonstrate that the genomic HRD is predictive of platinum response in a large cohort of TNBC PDX and identify alterations in XRCC3 and ORC1 genes driving cisplatin response.
(© 2023. The Author(s).)
Databáze: MEDLINE
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