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2 results on '"Catherine Carpentier"'

1. Identification of growth hormone receptor as a relevant target for precision medicine in low‐EGFR expressing glioblastoma

Author

Maïté Verreault, Irma Segoviano Vilchis, Shai Rosenberg, Nolwenn Lemaire, Charlotte Schmitt, Jérémy Guehennec, Louis Royer‐Perron, Jean‐Léon Thomas, TuKiet T. Lam, Florent Dingli, Damarys Loew, François Ducray, Sophie Paris, Catherine Carpentier, Yannick Marie, Florence Laigle‐Donadey, Audrey Rousseau, Natascha Pigat, Florence Boutillon, Franck Bielle, Karima Mokhtari, Stuart J. Frank, Aurélien deReyniès, Khê Hoang‐Xuan, Marc Sanson, Vincent Goffin, and Ahmed Idbaih

Subjects
cell migration, comparative analysis, glioblastoma, oncogenicity, pre‐clinical models, therapeutic target, Medicine (General), R5-920
Abstract

Abstract Objective New therapeutic approaches are needed to improve the prognosis of glioblastoma (GBM) patients. Methods With the objective of identifying alternative oncogenic mechanisms to abnormally activated epidermal growth factor receptor (EGFR) signalling, one of the most common oncogenic mechanisms in GBM, we performed a comparative analysis of gene expression profiles in a series of 54 human GBM samples. We then conducted gain of function as well as genetic and pharmocological inhibition assays in GBM patient‐derived cell lines to functionnally validate our finding. Results We identified that growth hormone receptor (GHR) signalling defines a distinct molecular subset of GBMs devoid of EGFR overexpression. GHR overexpression was detected in one third of patients and was associated with low levels of suppressor of cytokine signalling 2 (SOCS2) expression due to SOCS2 promoter hypermethylation. In GBM patient‐derived cell lines, GHR signalling modulates the expression of proteins involved in cellular movement, promotes cell migration, invasion and proliferation in vitro and promotes tumourigenesis, tumour growth, and tumour invasion in vivo. GHR genetic and pharmacological inhibition reduced cell proliferation and migration in vitro. Conclusion This study pioneers a new field of investigation to improve the prognosis of GBM patients.

Published
2022
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2. Prognostic Relevance of Histomolecular Classification of Diffuse Adult High-Grade Gliomas with Necrosis

Author

Gabriel Viennet, Pascale Varlet, Dominique Figarella-Branger, Anh Tuan Nguyen, Clovis Adam, Dominique Cazals-Hatem, Karima Mokhtari, Henri Sevestre, Fabien Forest, François Labrousse, Catherine Carpentier, Sandrine Eimer, Valérie Rigau, Danchristian Chiforeanu, Marie-Hélène Aubriot-Lorton, Carole Colin, Sophie Michalak, F. Vandenbos, Marie-Claire Tortel, Marie-Pierre Chenard, Annie Laquerrière, Isabelle Quintin-Roue, Pomone Richard, Anne Heitzmann, Delphine Loussouarn, Jean Louis Kemeny, Jean-Yves Delattre, Jean-Michel Vignaud, Caroline Dehais, Anne Jouvet, Emmanuelle Uro-Coste, Chiara Villa, Marie-Danièle Diebold, Pierre-Marie Levillain, Marc Polivka, Emmanuelle Lechapt-Zalcman, and Claude-Alain Maurage

Subjects
Pathology, medicine.medical_specialty, IDH1, Necrosis, Direct sequencing, General Neuroscience, Anaplastic oligodendroglioma, IDH1 R132H, Biology, IDH2, nervous system diseases, Pathology and Forensic Medicine, medicine, Neurology (clinical), Progression-free survival, Anaplastic Oligoastrocytoma, medicine.symptom
Abstract

Diffuse adult high-grade gliomas (HGGs) with necrosis encompass anaplastic oligodendrogliomas (AOs) with necrosis (grade III), glioblastomas (GBM, grade IV) and glioblastomas with an oligodendroglial component (GBMO, grade IV). Here, we aimed to search for prognostic relevance of histological classification and molecular alterations of these tumors. About 210 patients were included (63 AO, 56 GBM and 91 GBMO). GBMO group was split into "anaplastic oligoastrocytoma (AOA) with necrosis grade IV/GBMO," restricted to tumors showing intermingled astrocytic and oligodendroglial component, and "GBM/GBMO" based on tumors presenting oligodendroglial foci and features of GBM. Genomic arrays, IDH1 R132H expression analyses and IDH direct sequencing were performed. 1p/19q co-deletion characterized AO, whereas no IDH1 R132H expression and intact 1p/19q characterized both GBM and GBM/GBMO. AOA with necrosis/GBMO mainly demonstrated IDH1 R132H expression and intact 1p/19q. Other IDH1 or IDH2 mutations were extremely rare. Both histological and molecular classifications were predictive of progression free survival (PFS) and overall survival (OS) (P < 10(-4) ). Diffuse adult HGGs with necrosis can be split into three histomolecular groups of prognostic relevance: 1p/19q co-deleted AO, IDH1 R132H-GBM and 1p/19q intact IDH1 R132H+ gliomas that might be classified as IDH1 R132H+ GBM. Because of histomolecular heterogeneity, we suggest to remove the name GBMO.

Published
2014

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