Author: "Virginie Dangles-Marie" / Publication Year Range: Last 10 years - Searchworks@Jio Institute Digital Library Search Results

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33 results on '"Virginie Dangles-Marie"'

1. Spontaneous mouse lymphoma in patient-derived tumor xenografts: The importance of systematic analysis of xenografted human tumor tissues in preclinical efficacy trials

Author: Sophie Chateau-Joubert, Miriam Hopfe, Sophie Richon, Didier Decaudin, Sergio Roman-Roman, Edouard Reyes-Gomez, Ivan Bieche, Fariba Nemati, and Virginie Dangles-Marie
Subjects: Patient-derived tumor xenograft, Immunodeficient mice, Spontaneous mouse lymphoma, Experimental bias, Reproducibility of experimental results, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Patient-derived tumor xenograft (PDX) is now largely recognized as a key preclinical model for cancer research, mimicking patient tumor phenotype and genotype. Immunodeficient mice, well-known to develop spontaneous lymphoma, are required for PDX growth. As for all animal models used for further clinical translation, a robust experimental design is strongly required to lead to conclusive results. Here we briefly report unintentional co-engraftment of mouse lymphoma during expansion of well-established PDXs to illustrate the importance of systematic check of the PDX identity to avoid misinterpretation. Besides, this quality control based on complementary approaches deserves a more detailed description in materials and methods section to ensure experimental validity and reproducibility.
Published: 2021
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2. Array comparative genomic hybridization identifies high level of PI3K/Akt/mTOR pathway alterations in anal cancer recurrences

Author: Wulfran Cacheux, Petros Tsantoulis, Adrien Briaux, Sophie Vacher, Pascale Mariani, Marion Richard‐Molard, Bruno Buecher, Sophie Richon, Emmanuelle Jeannot, Julien Lazartigues, Etienne Rouleau, Odette Mariani, Elsy El Alam, Jérôme Cros, Sergio Roman‐Roman, Emmanuel Mitry, Elodie Girard, Virginie Dangles‐Marie, Astrid Lièvre, and Ivan Bièche
Subjects: anal squamous cell carcinoma, array comparative genomic hybridization, copy number alterations, PI3K/Akt/mTOR signaling pathway, somatic mutations, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Genomic alterations of anal squamous cell carcinoma (ASCC) remain poorly understood due to the rarity of this tumor. Array comparative genomic hybridization and targeted gene sequencing were performed in 49 cases of ASCC. The most frequently altered regions (with a frequency greater than 25%) were 10 deleted regions (2q35, 2q36.3, 3p21.2, 4p16.3, 4p31.21, 7q36.1, 8p23.3, 10q23.2, 11q22.3, and 13q14.11) and 8 gained regions (1p36.33, 1q21.1, 3q26.32, 5p15.33, 8q24.3, 9q34.3, 16p13.3, and 19p13.3). The most frequent minimal regions of deletion (55%) encompassed the 11q22.3 region containing ATM, while the most frequent minimal regions of gain (57%) encompassed the 3q26.32 region containing PIK3CA. Recurrent homozygous deletions were observed for 5 loci (ie, TGFR2 in 4 cases), and recurrent focal amplifications were observed for 8 loci (ie, DDR2 and CCND1 in 3 cases, respectively). Several of the focal amplified genes are targets for specific therapies. Integrated analysis showed that the PI3K/Akt/mTOR signaling pathway was the pathway most extensively affected, particularly in recurrences compared to treatment‐naive tumors (64% vs 30%; P = .017). In patients with ASCC recurrences, poor overall survival (OS) was significantly correlated with a large number of altered regions (P = .024). These findings provide insight into the somatic genomic alterations in ASCC and highlight the key role of the druggable PI3K/Akt/mTOR signaling pathway.
Published: 2018
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3. The early pregnancy placenta foreshadows DNA methylation alterations of solid tumors

Author: Akpéli V. Nordor, Djamel Nehar-Belaid, Sophie Richon, David Klatzmann, Dominique Bellet, Virginie Dangles-Marie, Thierry Fournier, and Martin J. Aryee
Subjects: cancer, dna methylation, epigenomics, epigenetics, hypomethylation, placenta, pregnancy, Genetics, QH426-470
Abstract: The placenta relies on phenotypes that are characteristic of cancer to successfully implant the embryo in the uterus during early pregnancy. Notably, it has to invade its host tissues, promote angiogenesis—while surviving hypoxia—, and escape the immune system. Similarities in DNA methylation patterns between the placenta and cancers suggest that common epigenetic mechanisms may be involved in regulating these behaviors. We show here that megabase-scale patterns of hypomethylation distinguish first from third trimester chorionic villi in the placenta, and that these patterns mirror those that distinguish many tumors from corresponding normal tissues. We confirmed these findings in villous cytotrophoblasts isolated from the placenta and identified a time window at the end of the first trimester, when these cells come into contact with maternal blood, as the likely time period for the methylome alterations. Furthermore, the large genomic regions affected by these patterns of hypomethylation encompass genes involved in pathways related to epithelial-mesenchymal transition, immune response, and inflammation. Analyses of expression profiles corresponding to genes in these hypomethylated regions in colon adenocarcinoma tumors point to networks of differentially expressed genes previously implicated in carcinogenesis and placentogenesis, where nuclear factor kappa B is a key hub. Taken together, our results suggest the existence of epigenetic switches involving large-scale changes of methylation in the placenta during pregnancy and in tumors during neoplastic transformation. The characterization of such epigenetic switches might lead to the identification of biomarkers and drug targets in oncology as well as in obstetrics and gynecology.
Published: 2017
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4. Spherical Cancer Models in Tumor Biology

Author: Louis-Bastien Weiswald, Dominique Bellet, and Virginie Dangles-Marie
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Three-dimensional (3D) in vitro models have been used in cancer research as an intermediate model between in vitro cancer cell line cultures and in vivo tumor. Spherical cancer models represent major 3D in vitro models that have been described over the past 4 decades. These models have gained popularity in cancer stem cell research using tumorospheres. Thus, it is crucial to define and clarify the different spherical cancer models thus far described. Here, we focus on in vitro multicellular spheres used in cancer research. All these spherelike structures are characterized by their well-rounded shape, the presence of cancer cells, and their capacity to be maintained as free-floating cultures. We propose a rational classification of the four most commonly used spherical cancer models in cancer research based on culture methods for obtaining them and on subsequent differences in sphere biology: the multicellular tumor spheroid model, first described in the early 70s and obtained by culture of cancer cell lines under nonadherent conditions; tumorospheres, a model of cancer stem cell expansion established in a serum-free medium supplemented with growth factors; tissue-derived tumor spheres and organotypic multicellular spheroids, obtained by tumor tissue mechanical dissociation and cutting. In addition, we describe their applications to and interest in cancer research; in particular, we describe their contribution to chemoresistance, radioresistance, tumorigenicity, and invasion and migration studies. Although these models share a common 3D conformation, each displays its own intrinsic properties. Therefore, the most relevant spherical cancer model must be carefully selected, as a function of the study aim and cancer type.
Published: 2015
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5. Supplementary Figure 1 from Characterization of a Large Panel of Patient-Derived Tumor Xenografts Representing the Clinical Heterogeneity of Human Colorectal Cancer

Author: Cyril Berthet, Olivier Duchamp, Sergio Roman-Roman, Patricia Vrignaud, Grégoire Prévost, Brigitte Demers, Loreley Calvet, Guillaume Lardier, Manoel Nunes, Hany Soliman, Hugues De Thé, Alain Pierré, Alain Bruno, Philippe Dessen, Bastien Job, Virginie Dangles-Marie, Patrick Gonin, Emmanuel Pham, Loïc Morgand, Denis Lantuas, Louis-Bastien Weiswald, Peggy Dartigues, Fariba Nemati, Ludovic Bigot, Sophie Landron, Pascale Mariani, Diane Goéré, Marc Pocard, Ludovic Lacroix, Ana Merino-Trigo, and Sylvia Julien
Abstract: PDF file, 156K, Histopathological characterization of the tumor samples.
Published: 2023
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6. Supplementary Figure 4 from Characterization of a Large Panel of Patient-Derived Tumor Xenografts Representing the Clinical Heterogeneity of Human Colorectal Cancer

Author: Cyril Berthet, Olivier Duchamp, Sergio Roman-Roman, Patricia Vrignaud, Grégoire Prévost, Brigitte Demers, Loreley Calvet, Guillaume Lardier, Manoel Nunes, Hany Soliman, Hugues De Thé, Alain Pierré, Alain Bruno, Philippe Dessen, Bastien Job, Virginie Dangles-Marie, Patrick Gonin, Emmanuel Pham, Loïc Morgand, Denis Lantuas, Louis-Bastien Weiswald, Peggy Dartigues, Fariba Nemati, Ludovic Bigot, Sophie Landron, Pascale Mariani, Diane Goéré, Marc Pocard, Ludovic Lacroix, Ana Merino-Trigo, and Sylvia Julien
Abstract: PDF file, 923K, Comparison of gene expression between primary tumor sample, early and late xenograft sample.
Published: 2023
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7. Supplementary Tables 1 - 4 from Characterization of a Large Panel of Patient-Derived Tumor Xenografts Representing the Clinical Heterogeneity of Human Colorectal Cancer

Author: Cyril Berthet, Olivier Duchamp, Sergio Roman-Roman, Patricia Vrignaud, Grégoire Prévost, Brigitte Demers, Loreley Calvet, Guillaume Lardier, Manoel Nunes, Hany Soliman, Hugues De Thé, Alain Pierré, Alain Bruno, Philippe Dessen, Bastien Job, Virginie Dangles-Marie, Patrick Gonin, Emmanuel Pham, Loïc Morgand, Denis Lantuas, Louis-Bastien Weiswald, Peggy Dartigues, Fariba Nemati, Ludovic Bigot, Sophie Landron, Pascale Mariani, Diane Goéré, Marc Pocard, Ludovic Lacroix, Ana Merino-Trigo, and Sylvia Julien
Abstract: PDF file, 129K, Table S1: Description of sequenced exons. Table S2: tumor growth observed in the first engraftment. Table S3: Tumor samples for which development of metastasis has been observed after an engraftment into the cecum. Table S4: Ontology analysis of gene differentially expressed between patient tumors and xenografts.
Published: 2023
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8. CCR Translation for This Article from Characterization of a Large Panel of Patient-Derived Tumor Xenografts Representing the Clinical Heterogeneity of Human Colorectal Cancer

Author: Cyril Berthet, Olivier Duchamp, Sergio Roman-Roman, Patricia Vrignaud, Grégoire Prévost, Brigitte Demers, Loreley Calvet, Guillaume Lardier, Manoel Nunes, Hany Soliman, Hugues De Thé, Alain Pierré, Alain Bruno, Philippe Dessen, Bastien Job, Virginie Dangles-Marie, Patrick Gonin, Emmanuel Pham, Loïc Morgand, Denis Lantuas, Louis-Bastien Weiswald, Peggy Dartigues, Fariba Nemati, Ludovic Bigot, Sophie Landron, Pascale Mariani, Diane Goéré, Marc Pocard, Ludovic Lacroix, Ana Merino-Trigo, and Sylvia Julien
Abstract: CCR Translation for This Article from Characterization of a Large Panel of Patient-Derived Tumor Xenografts Representing the Clinical Heterogeneity of Human Colorectal Cancer
Published: 2023
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9. Data from Characterization of a Large Panel of Patient-Derived Tumor Xenografts Representing the Clinical Heterogeneity of Human Colorectal Cancer

Author: Cyril Berthet, Olivier Duchamp, Sergio Roman-Roman, Patricia Vrignaud, Grégoire Prévost, Brigitte Demers, Loreley Calvet, Guillaume Lardier, Manoel Nunes, Hany Soliman, Hugues De Thé, Alain Pierré, Alain Bruno, Philippe Dessen, Bastien Job, Virginie Dangles-Marie, Patrick Gonin, Emmanuel Pham, Loïc Morgand, Denis Lantuas, Louis-Bastien Weiswald, Peggy Dartigues, Fariba Nemati, Ludovic Bigot, Sophie Landron, Pascale Mariani, Diane Goéré, Marc Pocard, Ludovic Lacroix, Ana Merino-Trigo, and Sylvia Julien
Abstract: Purpose: Patient-derived xenograft models are considered to represent the heterogeneity of human cancers and advanced preclinical models. Our consortium joins efforts to extensively develop and characterize a new collection of patient-derived colorectal cancer (CRC) models.Experimental Design: From the 85 unsupervised surgical colorectal samples collection, 54 tumors were successfully xenografted in immunodeficient mice and rats, representing 35 primary tumors, 5 peritoneal carcinoses and 14 metastases. Histologic and molecular characterization of patient tumors, first and late passages on mice includes the sequence of key genes involved in CRC (i.e., APC, KRAS, TP53), aCGH, and transcriptomic analysis.Results: This comprehensive characterization shows that our collection recapitulates the clinical situation about the histopathology and molecular diversity of CRC. Moreover, patient tumors and corresponding models are clustering together allowing comparison studies between clinical and preclinical data. Hence, we conducted pharmacologic monotherapy studies with standard of care for CRC (5-fluorouracil, oxaliplatin, irinotecan, and cetuximab). Through this extensive in vivo analysis, we have shown the loss of human stroma cells after engraftment, observed a metastatic phenotype in some models, and finally compared the molecular profile with the drug sensitivity of each tumor model. Through an experimental cetuximab phase II trial, we confirmed the key role of KRAS mutation in cetuximab resistance.Conclusions: This new collection could bring benefit to evaluate novel targeted therapeutic strategies and to better understand the basis for sensitivity or resistance of tumors from individual patients. Clin Cancer Res; 18(19); 5314–28. ©2012 AACR.
Published: 2023
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10. Supplementary Figure 2 from Characterization of a Large Panel of Patient-Derived Tumor Xenografts Representing the Clinical Heterogeneity of Human Colorectal Cancer

Author: Cyril Berthet, Olivier Duchamp, Sergio Roman-Roman, Patricia Vrignaud, Grégoire Prévost, Brigitte Demers, Loreley Calvet, Guillaume Lardier, Manoel Nunes, Hany Soliman, Hugues De Thé, Alain Pierré, Alain Bruno, Philippe Dessen, Bastien Job, Virginie Dangles-Marie, Patrick Gonin, Emmanuel Pham, Loïc Morgand, Denis Lantuas, Louis-Bastien Weiswald, Peggy Dartigues, Fariba Nemati, Ludovic Bigot, Sophie Landron, Pascale Mariani, Diane Goéré, Marc Pocard, Ludovic Lacroix, Ana Merino-Trigo, and Sylvia Julien
Abstract: PDF file, 241K, Frequency of abnormalities detected by aCGH among all samples tested across the genome.
Published: 2023
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11. Supplementary Figure 3 from Characterization of a Large Panel of Patient-Derived Tumor Xenografts Representing the Clinical Heterogeneity of Human Colorectal Cancer

Author: Cyril Berthet, Olivier Duchamp, Sergio Roman-Roman, Patricia Vrignaud, Grégoire Prévost, Brigitte Demers, Loreley Calvet, Guillaume Lardier, Manoel Nunes, Hany Soliman, Hugues De Thé, Alain Pierré, Alain Bruno, Philippe Dessen, Bastien Job, Virginie Dangles-Marie, Patrick Gonin, Emmanuel Pham, Loïc Morgand, Denis Lantuas, Louis-Bastien Weiswald, Peggy Dartigues, Fariba Nemati, Ludovic Bigot, Sophie Landron, Pascale Mariani, Diane Goéré, Marc Pocard, Ludovic Lacroix, Ana Merino-Trigo, and Sylvia Julien
Abstract: PDF file, 67K, Hierarchical clustering of 82 tumors based on Chromosomal abnormalities analyzed by 244k aCGH.
Published: 2023
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12. Supplementary Figure Legend from Characterization of a Large Panel of Patient-Derived Tumor Xenografts Representing the Clinical Heterogeneity of Human Colorectal Cancer

Author: Cyril Berthet, Olivier Duchamp, Sergio Roman-Roman, Patricia Vrignaud, Grégoire Prévost, Brigitte Demers, Loreley Calvet, Guillaume Lardier, Manoel Nunes, Hany Soliman, Hugues De Thé, Alain Pierré, Alain Bruno, Philippe Dessen, Bastien Job, Virginie Dangles-Marie, Patrick Gonin, Emmanuel Pham, Loïc Morgand, Denis Lantuas, Louis-Bastien Weiswald, Peggy Dartigues, Fariba Nemati, Ludovic Bigot, Sophie Landron, Pascale Mariani, Diane Goéré, Marc Pocard, Ludovic Lacroix, Ana Merino-Trigo, and Sylvia Julien
Abstract: PDF file, 72K.
Published: 2023
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13. Data from Establishment of Human Colon Cancer Cell Lines from Fresh Tumors versus Xenografts: Comparison of Success Rate and Cell Line Features

Author: Marie-France Poupon, Dominique Bellet, Françoise Praz, Bernard Dutrillaux, Pierre Validire, Nathalie Auger, Jean-Louis Janneau, Jean-Gabriel Judde, Patrick Saulnier, Franck Assayag, Louis-Bastien Weiswald, Sophie Richon, Marc Pocard, and Virginie Dangles-Marie
Abstract: Obtaining representative human colon cancer cell lines from fresh tumors is technically difficult. Using 32 tumor fragments from patients with colon cancer, the present study shows that prior xenograft leads to more efficient cell line establishment compared with direct establishment from fresh tumors (P < 0.05). From 26 tumor specimens, we successfully established 20 tumor xenografts in nude mice (77%); among 19 of these xenografts, 9 (47%) led to cell lines, including four from liver metastases. Only 3 of 31 tumor specimens (9.7%) grew immediately in vitro, and all were derived from primary tumors. To compare major phenotypic and genotypic characteristics of human colon cancer cell lines derived from the same tumor fragment using two protocols, the two pairs of cell lines obtained from 2 of 32 tumor fragments were extensively studied. They displayed similar morphology and were able to form compact spheroids. Chemosensitivity to 5-fluorouracil, CPT11, and L-OHP differed between cell lines obtained from patient tumors and those derived from xenografts. Matched cell lines shared a common core of karyotype alterations and distinctive additional chromosomal aberrations. Expression levels of genes selected for their role in oncogenesis evaluated by real-time quantitative PCR were found to be statistically correlated whatever the in vitro culture model used. In conclusion, xenotransplantation in mice of tumor fragments before establishment of cell lines enables generation of more novel human cancer cell lines for investigation of colon cancer cell biology, opening up the opportunity of reproducing the diversity of this disease. [Cancer Res 2007;67(1):398–407]
Published: 2023
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14. Supplementary Material and Methods from Establishment of Human Colon Cancer Cell Lines from Fresh Tumors versus Xenografts: Comparison of Success Rate and Cell Line Features

Author: Marie-France Poupon, Dominique Bellet, Françoise Praz, Bernard Dutrillaux, Pierre Validire, Nathalie Auger, Jean-Louis Janneau, Jean-Gabriel Judde, Patrick Saulnier, Franck Assayag, Louis-Bastien Weiswald, Sophie Richon, Marc Pocard, and Virginie Dangles-Marie
Abstract: Supplementary Material and Methods from Establishment of Human Colon Cancer Cell Lines from Fresh Tumors versus Xenografts: Comparison of Success Rate and Cell Line Features
Published: 2023
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15. Supplementary Table 1 from Evaluating Patient-Derived Colorectal Cancer Xenografts as Preclinical Models by Comparison with Patient Clinical Data

Author: Virginie Dangles-Marie, Ivan Bièche, Sergio Roman-Roman, Donald Bergstrom, James Watters, Weidong Zhang, Colette Dib, André Nicolas, Sophie Chateau-Joubert, Gerald Massonnet, Louis-Bastien Weiswald, Wulfran Cacheux, Astrid Lièvre, Sophie Richon, Sophie Vacher, Patricia Vrignaud, and Manoel Nunes
Abstract: Genomic alterations in KRAS/BRAF/NRA S wild-type xenografts, according to their response to cetuximab. Tumors were considered to be amplified if the gene copy number was >3. Gene overexpression is defined by an expression superior to average in all PDX panel + 1 SD.
Published: 2023
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16. Data from Evaluating Patient-Derived Colorectal Cancer Xenografts as Preclinical Models by Comparison with Patient Clinical Data

Author: Virginie Dangles-Marie, Ivan Bièche, Sergio Roman-Roman, Donald Bergstrom, James Watters, Weidong Zhang, Colette Dib, André Nicolas, Sophie Chateau-Joubert, Gerald Massonnet, Louis-Bastien Weiswald, Wulfran Cacheux, Astrid Lièvre, Sophie Richon, Sophie Vacher, Patricia Vrignaud, and Manoel Nunes
Abstract: Development of targeted therapeutics required translationally relevant preclinical models with well-characterized cancer genome alterations. Here, by studying 52 colorectal patient-derived tumor xenografts (PDX), we examined key molecular alterations of the IGF2–PI3K and ERBB–RAS pathways and response to cetuximab. PDX molecular data were compared with that published for patient colorectal tumors in The Cancer Genome Atlas. We demonstrated a significant pattern of mutual exclusivity of genomic abnormalities in the IGF2–PI3K and ERBB–RAS pathways. The genomic anomaly frequencies observed in microsatellite stable PDX reproduce those detected in nonhypermutated patient tumors. We found frequent IGF2 upregulation (16%), which was mutually exclusive with IRS2, PIK3CA, PTEN, and INPP4B alterations, supporting IGF2 as a potential drug target. In addition to maintaining the genomic and histologic diversity, correct preclinical models need to reproduce drug response observed in patients. Responses of PDXs to cetuximab recapitulate also clinical data in patients, with partial or complete response in 15% (8 of 52) of PDXs and response strictly restricted to KRAS wild-type models. The response rate reaches 53% (8 of 15) when KRAS, BRAF, and NRAS mutations are concomitantly excluded, proving a functional cross-validation of predictive biomarkers obtained retrospectively in patients. Collectively, these results show that, because of their clinical relevance, colorectal PDXs are appropriate tools to identify both new targets, like IGF2, and predictive biomarkers of response/resistance to targeted therapies. Cancer Res; 75(8); 1560–6. ©2015 AACR.
Published: 2023
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17. Supplementary Figure 2 from Evaluating Patient-Derived Colorectal Cancer Xenografts as Preclinical Models by Comparison with Patient Clinical Data

Author: Virginie Dangles-Marie, Ivan Bièche, Sergio Roman-Roman, Donald Bergstrom, James Watters, Weidong Zhang, Colette Dib, André Nicolas, Sophie Chateau-Joubert, Gerald Massonnet, Louis-Bastien Weiswald, Wulfran Cacheux, Astrid Lièvre, Sophie Richon, Sophie Vacher, Patricia Vrignaud, and Manoel Nunes
Abstract: Example of 2 PDXs treated with cetuximab (one red arrow for each injection).
Published: 2023
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18. Prognostic Value of

Author: Marc, Hilmi, Cindy, Neuzillet, Jérémie H, Lefèvre, Magali, Svrcek, Sophie, Vacher, Leonor, Benhaim, Peggy, Dartigues, Emmanuelle, Samalin, Julien, Lazartigues, Jean-François, Emile, Eugénie, Rigault, Nathalie, Rioux-Leclercq, Christelle, de La Fouchardière, David, Tougeron, Wulfran, Cacheux, Pascale, Mariani, Laura, Courtois, Matthieu, Delaye, Virginie, Dangles-Marie, Astrid, Lièvre, and Ivan, Bieche
Subjects: Adult, Aged, 80 and over, Male, Lung Neoplasms, Time Factors, Antineoplastic Agents, Exons, Middle Aged, ErbB Receptors, Mutagenesis, Insertional, Young Adult, Phenotype, Treatment Outcome, Drug Resistance, Neoplasm, Carcinoma, Non-Small-Cell Lung, Disease Progression, Humans, Female, Genetic Predisposition to Disease, Registries, Protein Kinase Inhibitors, Aged, Czech Republic, Retrospective Studies
Abstract: Per literature, patients with epidermal growth factor receptor (EGFR) exon-20 insertions respond poorly to tyrosine kinase inhibitors (TKIs). This study analyzed real-world data to examine the prognostic and predictive value of these mutations.We conducted a retrospective cohort study using Czech TULUNG Registry data, with data on multiple mutation types, collected in 2011-2020.We analyzed 554 (95.85%) patients with EGFR exon-19 deletions or exon-21 L858R substitutions and 24 (4.15%) patients with exon-20 insertions who received first-line high-value therapies. We summarized clinical characteristics and outcomes in all patients and by cohort. The risk of progression was statistically significantly higher (86%) in the exon-20 insertion cohort compared to the cohort with other mutations. Although not statistically significant, the risk of death was 44% higher in patients with exon-20 insertions.Advanced NSCLC patients with rare EGFR exon-20 insertions have a high risk of progression.
Published: 2021

19. Spontaneous mouse lymphoma in patient-derived tumor xenografts: The importance of systematic analysis of xenografted human tumor tissues in preclinical efficacy trials

Author: Fariba Nemati, Sergio Roman-Roman, Ivan Bièche, Miriam Hopfe, Edouard Reyes-Gomez, Didier Decaudin, Sophie Richon, Virginie Dangles-Marie, and Sophie Chateau-Joubert
Subjects: 0301 basic medicine, endocrine system, Cancer Research, endocrine system diseases, digestive system, 03 medical and health sciences, 0302 clinical medicine, Patient-derived tumor xenograft, Medicine, Reproducibility of experimental results, In patient, Tumor xenograft, RC254-282, Immunodeficient mice, business.industry, Mouse Lymphoma, Experimental bias, nutritional and metabolic diseases, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Experimental Bias, medicine.disease, Lymphoma, Human tumor, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Tumor phenotype, Perspective, Cancer research, business, Spontaneous mouse lymphoma, hormones, hormone substitutes, and hormone antagonists
Abstract: Highlights • Immunodeficient mice are susceptible to spontaneous tumors which are rarely reported in patient-derived tumor xenografts (PDX) studies. • Quality control of PDX identity is required at each step on the preclinical assays to avoid erroneous conclusions. • Description of the approaches used for this PDX check should be clearly detailed in material and methods section., Patient-derived tumor xenograft (PDX) is now largely recognized as a key preclinical model for cancer research, mimicking patient tumor phenotype and genotype. Immunodeficient mice, well-known to develop spontaneous lymphoma, are required for PDX growth. As for all animal models used for further clinical translation, a robust experimental design is strongly required to lead to conclusive results. Here we briefly report unintentional co-engraftment of mouse lymphoma during expansion of well-established PDXs to illustrate the importance of systematic check of the PDX identity to avoid misinterpretation. Besides, this quality control based on complementary approaches deserves a more detailed description in materials and methods section to ensure experimental validity and reproducibility., Graphical Abstract Image, graphical abstract
Published: 2021

20. Interaction between IGF2-PI3K axis and cancer-associated-fibroblasts promotes anal squamous carcinogenesis

Author: Anne Schnitzler, Adrien Briaux, Bruno Buecher, Pascale Mariani, Sergio Roman-Roman, Virginie Dangles-Marie, Rania El Botty, Jorge Barbazan, Ivan Bièche, Elsy El Alam, Astrid Lièvre, Sophie Richon, Wulfran Cacheux, and Sophie Vacher
Subjects: Cancer Research, animal structures, endocrine system diseases, biology, business.industry, medicine.medical_treatment, Anal Squamous Cell Carcinoma, medicine.disease_cause, female genital diseases and pregnancy complications, Targeted therapy, 03 medical and health sciences, Paracrine signalling, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Cancer-Associated Fibroblasts, Medicine, PTEN, business, Carcinogenesis, Protein kinase B, PI3K/AKT/mTOR pathway
Abstract: Anal squamous cell carcinoma (ASCC) is a rare tumour, but its incidence is increasing. Standard chemoradiotherapy fails to cure 20% of patients and no targeted therapy is currently approved for recurrent ASCC. The PI3K/Akt/mTOR pathway is frequently altered in this poorly characterised carcinoma. IGF2 was identified here as a key factor in ASCC oncogenesis, as IGF2 was shown to play a crucial role in the PI3K pathway with frequent (~60%) and mutually exclusive genomic alterations in IGF2, IGF1R, PTEN and PIK3CA genes. We also demonstrated that IGF2 expression is mainly due to cancer-associated fibroblasts and that IGF2 secreted by cancer-associated fibroblasts from ASCC samples promotes proliferation of a human ASCC cell line via IGF2 paracrine signalling. Altogether, these results highlight the key role of the IGF2/PI3K axis, and the major role of cancer-associated fibroblasts in tumour growth via IGF2 secretion, suggesting a major role of IGF2/IGF1R inhibitors in ASCC therapies.
Published: 2019
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21. Longitudinal high-resolution imaging through a flexible intravital imaging window

Author: Bethan Lloyd-Lewis, Didier Surdez, Silvia Fre, Aurélien Bore, Maria Benavente-Diaz, Virginie Dangles-Marie, Shahragim Tajbakhsh, Guillaume Jacquemin, Samir Djaber, Génétique et Biologie du Développement, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Cellules Souches et Développement / Stem Cells and Development, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Ecole Doctorale Complexité du Vivant (ED515), Sorbonne Université (SU), Plates-formes mutualisées du centre de recherche pharmaceutique de Paris (P-MIM - UMS 3612), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Bristol [Bristol], This work was supported by grants to S.F., B.L.-L., and G.J. from Paris Sciences et Lettres University (PSL Research University), the Institut Carnot, the French National Research Agency (ANR, grant no. ANR-15-CE13-0013-01), the Cancéropôle Île-de-France (grant no. 2015-2-APD-01-ICR-1), the Ligue contre le cancer (grant no. RS19/75-101), the LABEX DEEP ANR, number 11-LBX-0044, and by the 'FRM Equipes' EQU201903007821 and the FSER (La Fondation Schlumberger pour l’Education et la Recherche) FSER20200211117. The PICT-IBiSA facility is supported by the Fondation pour la Recherche Médicale (FRM no. DGE20111123020), the Cancéropôle Île-de-France (no. 2012-2-EML-04-IC-1), and the INCA (Cancer National Institute, no. 2011-1-LABEL-IC-4). D.S. and A.B. are supported by the Institut Curie SIRIC (Site de Recherche Intégrée en Cancérologie, INCa-DGOS-Inserm_12554, ITMO Cancer AVIESAN). B.L.-L. acknowledges support from the Academy of Medical Sciences, Wellcome Trust, and the University of Bristol. S.T. acknowledges funding support from the Institut Pasteur, Agence Nationale de la Recherche (Laboratoire d’Excellence Revive, Investissement d’Avenir, ANR-10-LABX-73), M.B.-D. was supported by the Laboratoire d’Excellence Revive and La Ligue Contre le cancer., ANR-15-CE13-0013,LumStemCell,Etude de la plasticité et du potentiel de différentiation des cellules souches luminales dans la glande mammaire pendant le développement et l'homéostasie adulte(2015), ANR-11-LABX-0044,DEEP,Développement, Epigénèse, Epigénétique et potentiel de vie(2011), ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), Gestionnaire, HAL Sorbonne Université 5, Etude de la plasticité et du potentiel de différentiation des cellules souches luminales dans la glande mammaire pendant le développement et l'homéostasie adulte - - LumStemCell2015 - ANR-15-CE13-0013 - AAPG2015 - VALID, Développement, Epigénèse, Epigénétique et potentiel de vie - - DEEP2011 - ANR-11-LABX-0044 - LABX - VALID, Laboratoires d'excellence - Stem Cells in Regenerative Biology and Medicine - - REVIVE2010 - ANR-10-LABX-0073 - LABX - VALID, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: [SDV.GEN]Life Sciences [q-bio]/Genetics, 0303 health sciences, Multidisciplinary, Materials science, integumentary system, ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION, SciAdv r-articles, Window (computing), [SDV.GEN] Life Sciences [q-bio]/Genetics, Cell Biology, Intravital Imaging, 03 medical and health sciences, 0302 clinical medicine, Research Methods, Implantation procedure, High resolution imaging, Research Articles, 030217 neurology & neurosurgery, Intravital microscopy, Preclinical imaging, Research Article, 030304 developmental biology, Biomedical engineering
Abstract: A fully flexible imaging window acting as an implantable transparent “second skin” upgrades in vivo imaging., Intravital microscopy (IVM) is a powerful technique that enables imaging of internal tissues at (sub)cellular resolutions in living animals. Here, we present a silicone-based imaging window consisting of a fully flexible, sutureless design that is ideally suited for long-term, longitudinal IVM of growing tissues and tumors. Crucially, we show that this window, without any customization, is suitable for numerous anatomical locations in mice using a rapid and standardized implantation procedure. This low-cost device represents a substantial technological and performance advance that facilitates intravital imaging in diverse contexts in higher organisms, opening previously unattainable avenues for in vivo imaging of soft and fragile tissues.
Published: 2021
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22. Array comparative genomic hybridization identifies high level of PI3K/Akt/mTOR pathway alterations in anal cancer recurrences

Author: Sergio Roman-Roman, Pascale Mariani, Ivan Bièche, Elodie Girard, Astrid Lièvre, Marion Richard-Molard, Elsy El Alam, Jérôme Cros, Sophie Vacher, Wulfran Cacheux, Adrien Briaux, Sophie Richon, Julien Lazartigues, Petros Tsantoulis, Emmanuel Mitry, Etienne Rouleau, Bruno Buecher, Odette Mariani, Emmanuelle Jeannot, and Virginie Dangles-Marie
Subjects: 0301 basic medicine, Cancer Research, Somatic cell, Biology, 03 medical and health sciences, 0302 clinical medicine, Cyclin D1, anal squamous cell carcinoma, medicine, Anal cancer, Radiology, Nuclear Medicine and imaging, Protein kinase B, Gene, PI3K/AKT/mTOR pathway, RC254-282, Original Research, Cancer Biology, copy number alterations, Anal Squamous Cell Carcinoma, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, array comparative genomic hybridization, Cancer research, somatic mutations, PI3K/Akt/mTOR signaling pathway, Comparative genomic hybridization
Abstract: Genomic alterations of anal squamous cell carcinoma (ASCC) remain poorly understood due to the rarity of this tumor. Array comparative genomic hybridization and targeted gene sequencing were performed in 49 cases of ASCC. The most frequently altered regions (with a frequency greater than 25%) were 10 deleted regions (2q35, 2q36.3, 3p21.2, 4p16.3, 4p31.21, 7q36.1, 8p23.3, 10q23.2, 11q22.3, and 13q14.11) and 8 gained regions (1p36.33, 1q21.1, 3q26.32, 5p15.33, 8q24.3, 9q34.3, 16p13.3, and 19p13.3). The most frequent minimal regions of deletion (55%) encompassed the 11q22.3 region containing ATM, while the most frequent minimal regions of gain (57%) encompassed the 3q26.32 region containing PIK3CA. Recurrent homozygous deletions were observed for 5 loci (ie, TGFR2 in 4 cases), and recurrent focal amplifications were observed for 8 loci (ie, DDR2 and CCND1 in 3 cases, respectively). Several of the focal amplified genes are targets for specific therapies. Integrated analysis showed that the PI3K/Akt/mTOR signaling pathway was the pathway most extensively affected, particularly in recurrences compared to treatment‐naive tumors (64% vs 30%; P = .017). In patients with ASCC recurrences, poor overall survival (OS) was significantly correlated with a large number of altered regions (P = .024). These findings provide insight into the somatic genomic alterations in ASCC and highlight the key role of the druggable PI3K/Akt/mTOR signaling pathway.
Published: 2018

23. 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

24. 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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25. Interaction between IGF2-PI3K axis and cancer-associated-fibroblasts promotes anal squamous carcinogenesis

Author: Wulfran, Cacheux, Astrid, Lièvre, Sophie, Richon, Sophie, Vacher, Elsy, El Alam, Adrien, Briaux, Rania, El Botty, Pascale, Mariani, Bruno, Buecher, Anne, Schnitzler, Jorge, Barbazan, Sergio, Roman-Roman, Ivan, Bièche, and Virginie, Dangles-Marie
Subjects: Male, Anus Neoplasms, Gene Expression Regulation, Neoplastic, Mice, Phosphatidylinositol 3-Kinases, Cancer-Associated Fibroblasts, Insulin-Like Growth Factor II, Cell Line, Tumor, Mutation, Paracrine Communication, Carcinoma, Squamous Cell, Animals, Humans, Female, Neoplasm Transplantation, Signal Transduction
Abstract: Anal squamous cell carcinoma (ASCC) is a rare tumour, but its incidence is increasing. Standard chemoradiotherapy fails to cure 20% of patients and no targeted therapy is currently approved for recurrent ASCC. The PI3K/Akt/mTOR pathway is frequently altered in this poorly characterised carcinoma
Published: 2018

26. Exome sequencing reveals aberrant signalling pathways as hallmark of treatment-naive anal squamous cell carcinoma

Author: Emmanuelle Jeannot, Astrid Lièvre, Virginie Dangles-Marie, Bruno Buecher, Julien Lazartigues, Wulfran Cacheux, Ivan Bièche, Thomas Rio-Frio, Odette Mariani, Etienne Rouleau, Fereshteh Farkhondeh, Marion Richard-Molard, Elodie Girard, Pascale Mariani, Nicolas Servant, S.R. Roman, Adrien Briaux, Emmanuel Mitry, Sophie Richon, Sophie Vacher, Jonchère, Laurent, CRLCC René Huguenin, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), 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), Centre de recherche de l'Institut Curie [Paris], Institut Curie [Paris], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Morphogénèse et Signalisation Cellulaires, Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Département de Recherche Translationnelle, Plateforme de sequencage ICGEX, Génétique, physiopathologie et approches thérapeutiques des maladies héréditaires du système nerveux (EA 7331), 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), Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Département de recherche translationnelle
Subjects: 0301 basic medicine, Somatic cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, medicine.disease_cause, whole exome sequencing, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, [SDV.CAN] Life Sciences [q-bio]/Cancer, anal squamous cell carcinoma, medicine, Exome sequencing, PI3K/AKT/mTOR pathway, Somatic mutation, Anal Squamous Cell Carcinoma, Cancer, Copy number alteration, medicine.disease, 3. Good health, 030104 developmental biology, Oncology, somatic mutation, copy number alteration, 030220 oncology & carcinogenesis, signalling pathway, Cancer research, Carcinogenesis, FAT1, Research Paper
Abstract: International audience; Anal squamous cell carcinomas (ASCC) are rare tumours in humans. The etiological role of HPV infection is now well established but little is known about the molecular landscape and signalling pathways involved in the pathogenesis of this cancer. Here we report the results from a whole exome sequencing of a homogeneous group of 20 treatment-naive ASCC. A total of 2422 somatic single nucleotide variations (SNV) were found, with an overall moderate rate of somatic mutations per tumour (median 105 relevant SNV per tumour) but a high mutational load in 3 tumours. The mutational signatures associated with age and APOBEC were observed in 100% and 60% of tumours respectively. The most frequently mutated genes were PIK3CA (25%) followed by FBXW7 (15%), FAT1 (15%), and TRIP12 (15%), the two last ones having never been described in ASCC. The main copy number alterations were gains of chromosome 3q (affecting PIK3CA) and losses of chromosome 11q (affecting ATM). The combined analysis of somatic mutations and copy number alterations show that recurrent alterations of the PI3K/AKT/mTOR pathway are frequent (60%) in these tumours, as well as potentially targetable alterations of other signalling pathways that have never been described in ASCC such as chromatin remodelling (45%) and ubiquitin mediated proteolysis (35%). These results highlight the possible implication of these aberrant signalling pathways in anal carcinogenesis and suggest promising new therapeutic approaches in ASCC. The high somatic mutation burden found in some tumours, suggesting an elevated neoantigen load could also predict sensitivity of ASCC to immunotherapy.
Published: 2017
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27. The early pregnancy placenta foreshadows dna methylation alterations of solid tumors

Author: David Klatzmann, Djamel Nehar-Belaid, Dominique Bellet, Thierry Fournier, Virginie Dangles-Marie, Martin J. Aryee, Akpeli V. Nordor, Sophie Richon, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), 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 Chimie du CNRS (INC), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Service de biothérapies [CHU Pitié-Salpétrière], Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Département de Recherche Translationnelle, Institut Curie [Paris], Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Université Paris Descartes - Paris 5 (UPD5), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Massachusetts General Hospital [Boston], 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)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], KLATZMANN, DAVID, CHU Pitié-Salpêtrière [AP-HP], 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Laboratoire de génétique moléculaire, Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), INSTITUT CURIE, La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus ( UMR_S 767 ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)
Subjects: 0301 basic medicine, Cancer Research, medicine.disease_cause, Epigenesis, Genetic, Pregnancy, ComputingMilieux_MISCELLANEOUS, Epigenomics, DNA methylation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, CANCER, 3. Good health, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Pregnancy Trimester, Second, embryonic structures, Chorionic villi, GROWTH, Female, Research Paper, GENES, placenta, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, 03 medical and health sciences, TROPHOBLAST, [SDV.CAN] Life Sciences [q-bio]/Cancer, INFLAMMATION, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Placenta, medicine, Humans, Neoplastic transformation, 5-METHYLCYTOSINE, Epigenetics, REGULATORY T-CELLS, Molecular Biology, PURIFICATION, epigenetics, Carcinoma, Placentation, Pregnancy Trimester, First, 030104 developmental biology, Immunology, epigenomics, Cancer research, HYPOMETHYLATED BLOCKS, IMPLANTATION, Carcinogenesis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, hypomethylation
Abstract: International audience; The placenta relies on phenotypes that are characteristic of cancer to successfully implant the embryo in the uterus during early pregnancy. Notably, it has to invade its host tissues, promote angiogenesis—while surviving hypoxia—, and escape the immune system. Similarities in DNA methylation patterns between the placenta and cancers suggest that common epigenetic mechanisms may be involved in regulating these behaviors. We show here that megabase-scale patterns of hypomethylation distinguish first from third trimester chorionic villi in the placenta, and that these patterns mirror those that distinguish many tumors from corresponding normal tissues. We confirmed these findings in villous cytotrophoblasts isolated from the placenta and identified a time window at the end of the first trimester, when these cells come into contact with maternal blood, as the likely time period for the methylome alterations. Furthermore, the large genomic regions affected by these patterns of hypomethylation encompass genes involved in pathways related to epithelial-mesenchymal transition, immune response, and inflammation. Analyses of expression profiles corresponding to genes in these hypomethylated regions in colon adenocarcinoma tumors point to networks of differentially expressed genes previously implicated in carcinogenesis and placentogenesis, where nuclear factor kappa B is a key hub. Taken together, our results suggest the existence of epigenetic switches involving large-scale changes of methylation in the placenta during pregnancy and in tumors during neoplastic transformation. The characterization of such epigenetic switches might lead to the identification of biomarkers and drug targets in oncology as well as in obstetrics and gynecology.
Published: 2017
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28. Interrogating open issues in cancer medicine with patient-derived xenografts

Author: Annette T. Byrne, Dominique Vanhecke, Laura Soucek, Sergio Roman-Roman, Alberto Villanueva, Elisabetta Marangoni, Eva Budinská, S. Gail Eckhardt, D Alferez, Enzo Medico, Gunhild Mari Mælandsmo, Andrew V. Biankin, Jos Jonkers, Daniel S. Peeper, Steven de Jong, Emilie Vinolo, Hans Clevers, Joaquín Arribas, Livio Trusolino, Virginie Dangles-Marie, Oscar M. Rueda, Alejandro Piris-Giménez, Robert Clarke, David K. Chang, Kristel Kemper, Monika A. Jarzabek, Eva González-Suárez, Els Hermans, Alejandra Bruna, Carlos Caldas, Joan Seoane, Pier Giuseppe Pelicci, Daniela Annibali, Jean-Christophe Marine, Jens Henrik Norum, Hector G. Palmer, Violeta Serra, Andrea Bertotti, George Coukos, Frédéric Amant, Manuel Hidalgo, Luisa Lanfrancone, Obstetrics and Gynaecology, Other departments, Amsterdam Reproduction & Development (AR&D), and Hubrecht Institute for Developmental Biology and Stem Cell Research
Subjects: 0301 basic medicine, medicine.medical_specialty, Published Erratum, business.industry, Applied Mathematics, General Mathematics, MEDLINE, Cancer, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Cancer Medicine, 030220 oncology & carcinogenesis, Family medicine, medicine, business
Abstract: Nature Reviews Cancer 17, 254–268 (2017) In the online html version of this article, Joan Seoane's affiliations were not correct. He is also a member of the EurOPDX Consortium and is at the Vall d'Hebron Institute of Oncology, 08035 Barcelona, the Universitat Autonoma de Barcelona, 08193 Bellaterra,and the Institucio Catalana de Recerca i Estudis Avancats (ICREA), 08010 Barcelona, Spain.
Published: 2017

29. Interrogating open issues in cancer precision medicine with patient-derived xenografts

Author: Livio Trusolino, Carlos Caldas, George Coukos, Dominique Vanhecke, Elisabetta Marangoni, Joan Seoane, Luisa Lanfrancone, Els Hermans, Monika A. Jarzabek, Eva González-Suárez, Jean-Christophe Marine, Laura Soucek, Sergio Roman-Roman, Enzo Medico, David K. Chang, Alejandro Piris-Giménez, Annette T. Byrne, Alejandra Bruna, Gunhild Mari Mælandsmo, Violeta Serra, Virginie Dangles-Marie, Andrew V. Biankin, Hans Clevers, Andrea Bertotti, Daniela Annibali, Kristel Kemper, Frédéric Amant, Steven de Jong, Pier Giuseppe Pelicci, Emilie Vinolo, Oscar M. Rueda, Daniel S. Peeper, Alberto Villanueva, Manuel Hidalgo, Jens Henrik Norum, Jos Jonkers, Héctor G. Palmer, D Alferez, Robert Clarke, S. Gail Eckhardt, Eva Budinská, Joaquín Arribas, and Hubrecht Institute for Developmental Biology and Stem Cell Research
Subjects: 0301 basic medicine, Cancer Research, Cancer therapy, Drug Resistance, Review, Bioinformatics, Tumour biomarkers, Mice, 0302 clinical medicine, Neoplasms, Medicine, Treatment resistance, Neoplasm Metastasis, Precision Medicine, Non-U.S. Gov't, Càncer, IN-VIVO, GENE-EXPRESSION, Cancer, Clinical Trials as Topic, Tumor, Applied Mathematics, Research Support, Non-U.S. Gov't, MOUSE MODEL, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Tumor markers, Neoplastic Stem Cells, Tumour immunology, Immunotherapy, Tumor immunology, hormones, hormone substitutes, and hormone antagonists, endocrine system, Tumour heterogeneity, General Mathematics, MEDLINE, Research Support, digestive system, N.I.H, 03 medical and health sciences, LUNG-CANCER, Cancer Medicine, Research Support, N.I.H., Extramural, Biomarkers, Tumor, Journal Article, NEGATIVE BREAST CANCERS, Animals, Humans, HEMATOPOIETIC STEM-CELLS, Cancer models, DUCTAL PANCREATIC-CANCER, business.industry, Animal, Marcadors tumorals, Extramural, Precision medicine, medicine.disease, Xenograft Model Antitumor Assays, CIRCULATING TUMOR-CELLS, Disease Models, Animal, METASTATIC COLORECTAL-CANCER, 030104 developmental biology, Drug Resistance, Neoplasm, Disease Models, Neoplasm, business, Biomarkers, ACQUIRED-RESISTANCE
Abstract: Patient-derived xenografts (PDXs) have emerged as an important platform to elucidate new treatments and biomarkers in oncology. PDX models are used to address clinically relevant questions, including the contribution of tumour heterogeneity to therapeutic responsiveness, the patterns of cancer evolutionary dynamics during tumour progression and under drug pressure, and the mechanisms of resistance to treatment. The ability of PDX models to predict clinical outcomes is being improved through mouse humanization strategies and the implementation of co-clinical trials, within which patients and PDXs reciprocally inform therapeutic decisions. This Opinion article discusses aspects of PDX modelling that are relevant to these questions and highlights the merits of shared PDX resources to advance cancer medicine from the perspective of EurOPDX, an international initiative devoted to PDX-based research.
Published: 2017

30. Specific detection of type II human chorionic gonadotropin beta subunit produced by trophoblastic and neoplastic cells

Author: A. Nordor, F. Troalen, L. Aldaz-Carroll, Virginie Dangles-Marie, Thierry Fournier, Melanie Cocquebert, A.-M. Hersant, Alain Pecking, B. Guery, Dominique Bellet, Sophie Richon, D. Stevens, Jean Guibourdenche, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), 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 Chimie du CNRS (INC), 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), Centre de recherche de l'Institut Curie [Paris], Institut Curie [Paris], Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Institut Gustave Roussy (IGR), Génétique (Biologie pathologie), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôpital René HUGUENIN (Saint-Cloud), Hôpital Renée Sabran [CHU - HCL], Hospices Civils de Lyon (HCL), 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)-Institut de Chimie du CNRS (INC)-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), and ORANGE, Colette
Subjects: [SDV]Life Sciences [q-bio], Clinical Biochemistry, Biochemistry, Human chorionic gonadotropin, 0302 clinical medicine, Pregnancy, Neoplasms, Gene expression, Chorionic Gonadotropin, beta Subunit, Human, TRANSCRIPTION, reproductive and urinary physiology, Immunoassay, 0303 health sciences, General Medicine, Immunohistochemistry, CANCER, 3. Good health, Trophoblasts, [SDV] Life Sciences [q-bio], PROGNOSTIC VALUE, medicine.anatomical_structure, 030220 oncology & carcinogenesis, embryonic structures, Female, hormones, hormone substitutes, and hormone antagonists, EXPRESSION, endocrine system, GENES, medicine.drug_class, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Monoclonal antibody, 03 medical and health sciences, Syncytiotrophoblast, [SDV.CAN] Life Sciences [q-bio]/Cancer, Placenta, Cell Line, Tumor, medicine, Humans, ASSAYS, FAMILIAL HCG SYNDROME, 030304 developmental biology, Biochemistry, medical, Biochemistry (medical), Trophoblast, Molecular biology, EVOLUTION, ALPHA, MRNA Sequencing, Down Syndrome, MONOCLONAL-ANTIBODIES, Gonadotropins
Abstract: International audience; Background: The sequence of the beta-subunit of human chorionic gonadotropin (hCG beta varies depending on whether hCG beta is encoded by type I or type II genes. Type II genes are upregulated in trophoblast and cancer but hCG beta can be detected in the serum of nonpregnant women and healthy individuals. We aimed to determine whether monoclonal antibody (mAb) FBT11-II specifically detects hCG beta encoded by type II genes (type II hCG beta). Methods: Competitive inhibition assays with synthetic peptides, immunocytochemical and immunohistochemical studies, type II hCG beta dosing immunoassays and sequencing of CGB genes were performed. Results: Competitive inhibition assays determined that mAb FBT11-II recognizes the type II hCG beta derived peptide. CGB mRNA sequencing of JEG-3 (trophoblastic) and 124 (bladder) cell lines confirmed that JEG-3 expresses type II genes while T24 expresses exclusively type I. FBT11-II only recognizes JEG-expressed hCG beta. Placenta immunohistochemical studies confirmed that type II hCG beta expression is restricted to the syncytiotrophoblast. Immunoassays detected type II hCG beta in serum of patients with either nontrophoblastic cancers or fetal Down syndrome. Conclusion: Type II gene expression can be detected using FBT11-II. This specific recognition could improve the clinical usefulness of assays aimed at either managing aggressive tumors or screening for Down syndrome.
Published: 2015
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31. Abstract IA05: PDX in colorectal cancer and carcinoma of the anal canal

Author: Virginie Dangles-Marie
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Pathology, business.industry, Colorectal cancer, Anal Squamous Cell Carcinoma, Cancer, Anal canal, medicine.disease, Metastasis, Efficacy, medicine.anatomical_structure, Internal medicine, medicine, Carcinoma, business, Ex vivo
Abstract: Through 2 examples of digestive tumors, (colorectal cancer, “CRC”, and anal squamous cell carcinoma, “ASCC”), we will present the development and use of patient-derived tumor xenografts. Colorectal cancer remains a major cause of mortality worldwide and CRC patient death is generally attributable to metastasis development. By contrast, ASCC is a rare tumor (< 5% of all lower gastrointestinal tract malignancies in Europe) but with increasing incidence and mutilating surgery for patients with chemoradiotherapy-resistant tumors. Consequently, these both digestive tumors require new therapeutic approaches and relevant preclinical models to identify and test new drugs/combinations. In this context, we develop and characterize patient-derived CRC and ASCC xenografts. We will illustrate the capacity of these PDXs to recapitulate the intratumoral clonal heterogeneity, gene expression profile, key molecular alterations, histology and drug response of the patient tumors through passages in mice. In addition to these now well-known features depicted in a large number of tumor types, we will discuss about practical situations (orthotopic engraftment, impact of mouse host, criteria for measuring drug efficacy). Finally, we will report alternative methods as ex vivo tumor spheres we have developed. Citation Format: Virginie Dangles-Marie. PDX in colorectal cancer and carcinoma of the anal canal. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr IA05.
Published: 2016
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32. Abstract 2762: Common DNA methylation patterns in cancer and placental cells involved in migration and invasion, immune escape, and angiogenesis induction

Author: Thierry Fournier, Dominique Bellet, Martin J. Aryee, Virginie Dangles-Marie, Sophie Richon, and Akpeli V. Nordor
Subjects: Cancer Research, Angiogenesis, Biology, medicine.disease, Primary tumor, Metastasis, medicine.anatomical_structure, Oncology, Placenta, Immunology, DNA methylation, Cancer research, medicine, Cytotrophoblasts, Epigenetics, Epigenomics
Abstract: Identifying common patterns of regulation in cancer and placental cells might shed new light on cellular programs allowing aggressive tumor development. Indeed, as it has been described for the first time more than a century ago, cancer and placental cells (trophoblasts) share astonishingly similar phenotypes : migration and invasion, immune escape, and angiogenesis induction. These common phenotypes, relying on common genomic sequences and transcriptomic profiles, may result from a shared epigenomic regulation program. This might be especially true for tumor cells leading eventually to metastasis and cytotrophoblasts (a trophoblasts subset) during placental implantation at the beginning of pregnancy. In order to investigate such common epigenomic patterns, we carried out comparisons of DNA methylation in cancer and placental cell genomes. This study involved: cancer samples (primary tumor vs. normal tissue) across various tissues (including breast, colon, liver, lung, prostate, thyroid, uterus), on one hand; and placenta samples (early vs. late term) either heterogeneous (chorionic villi) or homogenous (ex vivo cytotrophoblasts), on the other hand. Cancer data were data downloaded from The Cancer Genome Atlas web portal. Placenta data were downloaded from the Gene Expression Omnibus web portal. In addition, our group generated original data from ex vivo cytotrophoblasts samples. All data were generated on the Illumina Infinium 450K array. Data analysis was carried out thanks to computational methods for epigenomics recently described. This first direct comparison of cancer and placental cells epigenomes, leveraging both published data and original data, led to the identification of large hypomethylated blocks common to cancer and placental cells. Such common patterns have recently been described as a universal defining epigenetic alteration in human solid tumors. These megabase-scale DNA methylation marks differentiate primary tumors from normal tissues. Likewise, they differentiate early term placentas from late term placentas. Moreover, genes belonging to genomic regions displaying common large hypomethylated blocks overlapping in cancers and placentas are enriched for pathways involved in migration and invasion, immune escape, and angiogenesis induction. Common DNA methylation patterns in cancer and placental cells identified in this pilot study might contribute to the epigenomic regulation of cellular programs allowing aggressive tumor development. Further analyses of these common patterns, as well as analyses of differences in cancer and placental cell epigenomes, could eventually lead to the identification of critical epigenomic switches that prevent healthy placentas to degenerate into tumors, while they allow aggressive tumors to develop. Ultimately, such epigenomic switches could also represent innovative targets in oncology. Citation Format: Akpeli V. Nordor, Sophie Richon, Thierry Fournier, Dominique Bellet, Virginie Dangles-Marie, Martin J. Aryee. Common DNA methylation patterns in cancer and placental cells involved in migration and invasion, immune escape, and angiogenesis induction. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2762.
Published: 2016
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33. PI3KCA mutation as an independent pronostic factor in anal squamous cell carcinoma treated by abdomino-perineal resection: Evidence from a retrospective cohort of 148 patients

Author: Arnaud Roth, Wulfran Cacheux, Adrien Briaux, Fereshteh Farkhondeh, Sophie Richon, Anne de la Rochefordière, Julien Lazartigues, Astrid Lièvre, Marie-Christine Falcou, Petros Tsantoulis, Sergio Roman-Roman, Virginie Dangles-Marie, Pascale Mariani, Emmanuel Mitry, Ivan Bièche, Emmanuelle Jeannot, Marion Richard-Molard, Bruno Buecher, and Etienne Rouleau
Subjects: Oncology, Cancer Research, medicine.medical_specialty, business.industry, Internal medicine, Mutation (genetic algorithm), Anal Squamous Cell Carcinoma, Medicine, Retrospective cohort study, Molecular Profile, Abdomino perineal resection, business
Abstract: e15060Background: A better understanding of the molecular profile of the anal squamous cell carcinomas (ASCCs) is necessary to consider new therapeutic approaches, and the identification of prognos...
Published: 2016
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33 results on '"Virginie Dangles-Marie"'

1. Spontaneous mouse lymphoma in patient-derived tumor xenografts: The importance of systematic analysis of xenografted human tumor tissues in preclinical efficacy trials

2. Array comparative genomic hybridization identifies high level of PI3K/Akt/mTOR pathway alterations in anal cancer recurrences

3. The early pregnancy placenta foreshadows DNA methylation alterations of solid tumors

4. Spherical Cancer Models in Tumor Biology

5. Supplementary Figure 1 from Characterization of a Large Panel of Patient-Derived Tumor Xenografts Representing the Clinical Heterogeneity of Human Colorectal Cancer

6. Supplementary Figure 4 from Characterization of a Large Panel of Patient-Derived Tumor Xenografts Representing the Clinical Heterogeneity of Human Colorectal Cancer

7. Supplementary Tables 1 - 4 from Characterization of a Large Panel of Patient-Derived Tumor Xenografts Representing the Clinical Heterogeneity of Human Colorectal Cancer

8. CCR Translation for This Article from Characterization of a Large Panel of Patient-Derived Tumor Xenografts Representing the Clinical Heterogeneity of Human Colorectal Cancer

9. Data from Characterization of a Large Panel of Patient-Derived Tumor Xenografts Representing the Clinical Heterogeneity of Human Colorectal Cancer

10. Supplementary Figure 2 from Characterization of a Large Panel of Patient-Derived Tumor Xenografts Representing the Clinical Heterogeneity of Human Colorectal Cancer

11. Supplementary Figure 3 from Characterization of a Large Panel of Patient-Derived Tumor Xenografts Representing the Clinical Heterogeneity of Human Colorectal Cancer

12. Supplementary Figure Legend from Characterization of a Large Panel of Patient-Derived Tumor Xenografts Representing the Clinical Heterogeneity of Human Colorectal Cancer

13. Data from Establishment of Human Colon Cancer Cell Lines from Fresh Tumors versus Xenografts: Comparison of Success Rate and Cell Line Features

14. Supplementary Material and Methods from Establishment of Human Colon Cancer Cell Lines from Fresh Tumors versus Xenografts: Comparison of Success Rate and Cell Line Features

15. Supplementary Table 1 from Evaluating Patient-Derived Colorectal Cancer Xenografts as Preclinical Models by Comparison with Patient Clinical Data

16. Data from Evaluating Patient-Derived Colorectal Cancer Xenografts as Preclinical Models by Comparison with Patient Clinical Data

17. Supplementary Figure 2 from Evaluating Patient-Derived Colorectal Cancer Xenografts as Preclinical Models by Comparison with Patient Clinical Data

18. Prognostic Value of

19. Spontaneous mouse lymphoma in patient-derived tumor xenografts: The importance of systematic analysis of xenografted human tumor tissues in preclinical efficacy trials

20. Interaction between IGF2-PI3K axis and cancer-associated-fibroblasts promotes anal squamous carcinogenesis

21. Longitudinal high-resolution imaging through a flexible intravital imaging window

22. Array comparative genomic hybridization identifies high level of PI3K/Akt/mTOR pathway alterations in anal cancer recurrences

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

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

25. Interaction between IGF2-PI3K axis and cancer-associated-fibroblasts promotes anal squamous carcinogenesis

26. Exome sequencing reveals aberrant signalling pathways as hallmark of treatment-naive anal squamous cell carcinoma

27. The early pregnancy placenta foreshadows dna methylation alterations of solid tumors

28. Interrogating open issues in cancer medicine with patient-derived xenografts

29. Interrogating open issues in cancer precision medicine with patient-derived xenografts

30. Specific detection of type II human chorionic gonadotropin beta subunit produced by trophoblastic and neoplastic cells

31. Abstract IA05: PDX in colorectal cancer and carcinoma of the anal canal

32. Abstract 2762: Common DNA methylation patterns in cancer and placental cells involved in migration and invasion, immune escape, and angiogenesis induction

33. PI3KCA mutation as an independent pronostic factor in anal squamous cell carcinoma treated by abdomino-perineal resection: Evidence from a retrospective cohort of 148 patients

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33 results on '"Virginie Dangles-Marie"'

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