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    Team : Endocrine tumors and signaling

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    Team leader :

     

    Our laboratory works on endocrine tumors. We are particularly interested in the pathogenesis of tumors of the adrenal cortex, thyroid and pituitary .

     

    The study of familial multiple endocrine neoplasias, has identified some of the signaling pathways responsible for endocrine tumorigenesis. Molecular abnormalities involving actors of the cyclic AMP signaling pathway are frequently observed in endocrine tumors. Carney complex, a rare form of multiple endocrine neoplasia responsible for pituitary, thyroid, adrenal and gonadal tumors is due to mutations of a regulatory subunit of protein kinase A (PKA). Our work lead to a better understanding of the disease and the role of PKA in adrenocortical tumors causing Cushing's syndrome (excessive secretion of cortisol) and to identify new genes involved cAMP pathway in the development of these tumors.

     

    We are also interested in these endocrine tumors to other signaling pathways involved in other types of cancer. We were able to demonstrate for the first time the central role of mutations of ß-catenin (CTNNB1) in benign and malignant tumors of the adrenal cortex. Abnormalities of the MAPK pathway also play a role in endocrine tumors, and differentiated thyroid cancers represent an excellent model to study this pathway. Activating mutations of the BRAF oncogene powerful are present in about 50% of papillary thyroid cancers. We are studying the determinants of the activation of the MAPK pathway in thyroid carcinogenesis.

     

    We have made progress in recent years in the molecular classification of tumors of the adrenal cortex by genomic approaches. One of our goals is the integrated genomic analysis of tumors of the adrenal in theCarte d’Identité des Tumors program of the Ligue Contre le Cancer. This allows us to make progress on the pathophysiology but also to identify diagnostic and prognostic markers of adrenal cancers that eventually will guide patient management. We currently use the powerful tool of genomics, especially next generation sequencing in the context of genomics platform of the Cochin Institute, to identify new somatic molecular abnormalities in sporadic endocrine cancer and new genes responsible for familial forms of adrenal tumors. These genomic approaches are also used to understand the mechanisms of dysregulation of the signaling pathways that we study in in vitro models of endocrine tumors .

     

    All this work is done in close interaction with clinical services from Cochin and HEGP Hospital ( referral center for rare adrenal diseases, expert INCA rare adrenal cancer center, expert center for thyroid cancer .... ) and through national and international research networks dedicated to endocrine tumors ( COMETE, ENS@T ..... ).