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2 results on '"Virginie Dangles-Marie"'

1. Clinical value of R-spondins in triple-negative and metaplastic breast cancers

Author

R. El Botty, Sergio Roman-Roman, Martial Caly, Thierry Dubois, Laetitia Fuhrmann, Sophie Vacher, Ivan Bièche, Florence Coussy, Sophie Richon, Elisabetta Marangoni, André Nicolas, Walid Chemlali, Anne Schnitzler, François Lallemand, Virginie Dangles-Marie, Ludmilla Deplater, and Didier Meseure

Subjects
0301 basic medicine, Cancer Research, Small interfering RNA, Gene Expression, Triple Negative Breast Neoplasms, Receptors, G-Protein-Coupled, RNA, Small Interfering, Wnt Signaling Pathway, Carcinoma, Ductal, Breast, Wnt signaling pathway, targeted therapy, Blot, Oncology, Quinolines, Intercellular Signaling Peptides and Proteins, Female, medicine.medical_specialty, Mice, Nude, Antineoplastic Agents, triple-negative and metaplastic breast cancers, Imides, 03 medical and health sciences, Internal medicine, Wnt3A Protein, medicine, Wnt/β-catenin pathway, Animals, Humans, RNA, Messenger, RSPO2, Molecular Diagnostics, Cell Proliferation, Metaplasia, Cell growth, business.industry, HEK 293 cells, Cancer, medicine.disease, TATA-Box Binding Protein, 030104 developmental biology, Endocrinology, HEK293 Cells, Cell culture, Culture Media, Conditioned, Cancer research, prognosis, R-spondins, business, Thrombospondins, Neoplasm Transplantation
Abstract

Background: RSPO ligands, activators of the Wnt/β-catenin pathway, are overexpressed in different cancers. The objective of this study was to investigate the role of RSPOs in breast cancer (BC). Methods: Expression of RSPO and markers of various cancer pathways were measured in breast tumours and cell lines by qRT–PCR. The effect of RSPO on the Wnt/β-catenin pathway activity was determined by luciferase assay, western blotting, and qRT–PCR. The effect of RSPO2 inhibition on proliferation was determined by using RSPO2 siRNAs. The effect of IWR-1, an inhibitor of the Wnt/β-catenin pathway, was examined on the growth of an RSPO2-positive patient-derived xenograft (PDX) model of metaplastic triple-negative BC. Results: We detected RSPO2 and RSPO4 overexpression levels in BC, particularly in triple-negative BC (TNBC), metaplastic BC, and triple-negative cell lines. Various mechanisms could account for this overexpression: presence of fusion transcripts involving RSPO, and amplification or hypomethylation of RSPO genes. Patients with RSPO2-overexpressing tumours have a poorer metastasis-free survival (P=3.6 × 10−4). RSPO2 and RSPO4 stimulate Wnt/β-catenin pathway activity. Inhibition of RSPO expression in a TN cell line inhibits cell growth, and IWR-1 significantly inhibits the growth of an RSPO2-overexpressing PDX. Conclusions: RSPO overexpression could therefore be a new prognostic biomarker and therapeutic target for TNBC.

Published
2017

2. Mutational analysis of anal cancers demonstrates frequent PIK3CA mutations associated with poor outcome after salvage abdominoperineal resection

Author

Sophie Richon, Marie-Christine Falcou, Emmanuel Mitry, Xavier Sastre-Garau, Adrien Briaux, Julien Lazartigues, Wulfran Cacheux, Fereshteh Farkhondeh, Etienne Rouleau, Petros Tsantoulis, Arnaud Roth, Emmanuelle Jeannot, Virginie Dangles-Marie, Bruno Buecher, Anne de la Rochefordière, Pascale Mariani, Sergio Roman-Roman, Ivan Bièche, Marion Richard-Molard, D. Stevens, Astrid Lièvre, A. Labib, Laboratoire d'Oncogénétique, CRLCC René Huguenin, Institut Curie [Paris], Département de chirurgie, Service de Génétique Oncologique, Département de Recherche Translationnelle, Centre de Recherche, Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-Institut Curie [Paris], Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux (Inserm U745), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Compartimentation et dynamique cellulaires (CDC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Biostatistique, Facultés des sciences pharmaceutiques et biologiques, Service des Maladies de l'Appareil Digestif, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Pontchaillou [Rennes], CEST (Comite d'Evaluation et de Suivi des projets de recherche de Transfert) from the Institut Curie, Institut Curie, Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-PRES Sorbonne Paris Cité, Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-PRES Sorbonne Paris Cité, Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Service des Maladies de l'Appareil Digestif [CHU Rennes], INSTITUT CURIE, Université Paris Descartes - Paris 5 ( UPD5 ) -PRES Sorbonne Paris Cité-INSTITUT CURIE, Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux ( Inserm U745 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Compartimentation et dynamique cellulaires ( CDC ), Centre National de la Recherche Scientifique ( CNRS ) -INSTITUT CURIE-Université Pierre et Marie Curie - Paris 6 ( UPMC ), Université de Rennes 1 ( UR1 ), and Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes]

Subjects
0301 basic medicine, Neuroblastoma RAS viral oncogene homolog, Oncology, Male, Cancer Research, medicine.medical_treatment, DNA Mutational Analysis, growth-factor-receptor, medicine.disease_cause, human-papillomavirus, chemoradiotherapy, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, anal squamous cell carcinoma, prognostic factor, abdominoperineal resection, Cervical cancer, Aged, 80 and over, Abdominoperineal resection, epidermoid carcinoma, therapeutic target, Middle Aged, Anus Neoplasms, 3. Good health, Epidermoid carcinoma, 030220 oncology & carcinogenesis, Female, KRAS, Adult, medicine.medical_specialty, Class I Phosphatidylinositol 3-Kinases, chemoradiation therapy, mutation status, survival, 03 medical and health sciences, Internal medicine, expression, medicine, Humans, HRAS, neoplasms, Molecular Diagnostics, Aged, Retrospective Studies, cervical-cancer, Salvage Therapy, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, squamous-cell carcinoma, PIK3CA, medicine.disease, Radiation therapy, 030104 developmental biology, comprehensive molecular characterization, Mutation, Neoplasm Recurrence, Local, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, business, Chemoradiotherapy
Abstract

International audience; Background: A better understanding of the molecular profile of anal squamous cell carcinomas (ASCCs) is necessary to consider new therapeutic approaches, and the identification of prognostic and predictive factors for response to treatment. Methods: We retrospectively analysed tumours from ASCC patients for mutational analysis of KRAS, NRAS, HRAS, BRAF, PIK3CA, MET, TP53 and FBXW7 genes by HRM and Sanger sequencing analysis. Results: Specimens from 148 patients were analysed: 96 treatment-naive tumours and 52 recurrences after initial radiotherapy (RT) or chemoradiotherapy (CRT). Mutations of KRAS, PIK3CA, FBXW7 and TP53 genes were present in 3 (2.0%), 30 (20.3%), 9 (6.1%) and 7 tumours (4.7%), respectively. The distribution of the mutations was similar between treatment-naive tumours and recurrences, except for TP53 mutations being more frequent in recurrences (P = 0.0005). In patients treated with abdominoperineal resection (APR) after relapse (n = 38, median follow-up of 18.2 years), overall survival (OS) was significantly correlated with HPV16 status (P = 0.048), gender (P = 0.045) and PIK3CA mutation (P = 0.037). The PIK3CA status retained its prognostic significance in Cox multivariate regression analysis (P = 0.025). Conclusions: Our study identified PIK3CA mutation as an independent prognostic factor in patients who underwent APR for ASCC recurrence, suggesting a potential benefit from adjuvant treatment and the evaluation of targeted therapies with PI3K/Akt/mTor inhibitors in PIK3CA-mutated patients.

Published
2016
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