Position: Inserm Research Director, class 2.
Inserm U830 « Genetics and biology of cancers »
Institut Curie, Centre de Recherche, 26 rue d'Ulm
75248 Paris Cedex 05 FRANCE
Tél. : 33 1 56 24 66 84
E-mail : email@example.com
Training and positions
Neuroblastoma (NB) is an embryonal cancer of the sympathetic nervous system observed in early childhood and characterized by a broad spectrum of clinical behaviors, ranging from spontaneous regression to fatal outcome despite aggressive therapies. NB accounts for 8-10% of pediatric cancers and 15% of the deaths attributable to malignant conditions in children. The outcome of children with aggressive NB remains poor with long-term survival rates still lower than 40%. In order to improve the prognosis of this pediatric cancer and to identify new therapeutic targets, a better understanding of the mechanisms and genes implicated in oncogenesis is required. Interestingly, NB may occur in various contexts, being mostly sporadic but also familial and/or syndromic.
My research program aims at identifying the genes and mechanisms involved in NB development and/or progression and to characterize the genes linked to tumor predisposition. In 2008, we characterized somatic and germline gain-of-function mutations of the ALK (Anaplastic Lymphoma Kinase) gene, encoding a tyrosine kinase receptor, in sporadic and familial NB cases. Our data also provided a strong molecular rationale for ALK targeted therapy in NB. My project focuses on two main aspects: (1) characterization of the molecular mechanisms associated with ALK alterations in NB oncogenesis; (2) identification of other genes implicated in the neoplastic transformation.
In order to further determine the implication of the ALK gene in NB oncogenesis, we have started an extensive characterization of the ALK locus at the genomic level. Moreover, we also develop ALK Knock-In mice, with the aim to investigate the role of ALK in physiological conditions and determine the oncogenic properties of ALK mutated receptors. Furthermore, we plan to identify additional genes involved in NB sporadic tumors and/or tumor predisposition by using Next Generation Sequencing, including mate-pair analysis to characterize genomic rearrangements and exome or whole-genome sequencing. Altogether, these approaches should increase our knowledge of NB biology and identify new driver mutations in NB oncogenesis.