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    Genomics and epigenetics of rare tumors.

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      Team leader:

     

    Our main research projects are dedicated to the study of rare tumor-predisposition syndromes and their associated cancerous (malignant) and noncancerous (benign) tumors. Our team is interested in (1) the genetic and cellular mechanisms involved in the development of these pathologies, and (2) the genomics and therapeutic targeting of the associated tumors.

     

    Objectives

    The main interests of our group are:

    1. The study of genetic and epigenetic of cancer-predisposition disorders. We aim at understanding the mechanisms underlying the variable expressivity (study of genotype-phenotype correlations, and identification of modifier genes) and the genetic heterogeneity of rare hereditary tumor syndromes, including neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis, and polymerase proofreading-associated polyposis (PPAP);
    2. The functional characterization of NF1-driven tumors to identify the key drivers of tumorigenesis, and their targeting.

     

    Main Publications

    Wassef M, Luscan A, Aflaki S, Zielinski D, Jansen PWTC, Baymaz HI, Battistella A, Kersouani C, Servant N, Wallace MR, Romero P, Kosmider O, Just PA, Hivelin M, Jacques S, Vincent-Salomon A, Vermeulen M, Vidaud M, Pasmant E*, Margueron R*. EZH1/2 function mostly within canonical PRC2 and exhibit proliferation-dependent redundancy that shapes mutational signatures in cancer. Proc Natl Acad Sci U S A. 2019. *corresponding authors (https://www.ncbi.nlm.nih.gov/pubmed/30867289)

     

    Shackleford G, Sampathkumar NK, Hichor M, Weill L, Meffre D, Juricek L, Laurendeau I, Chevallier A, Ortonne N, Larousserie F, Herbin M, Bièche I, Coumoul X, Beraneck M, Baulieu EE, Charbonnier F, Pasmant E, Massaad C. Involvement of Aryl hydrocarbon receptor in myelination and in human nerve sheath tumorigenesis. Proc Natl Acad Sci U S A. 2018;115:E1319-E1328. (https://www.ncbi.nlm.nih.gov/pubmed/29351992)

     

    Lantieri L, Grimbert P, Ortonne N, Suberbielle C, Bories D, Gil-Vernet S, Lemogne C, Bellivier F, Lefaucheur JP, Schaffer N, Martin F, Meningaud JP, Wolkenstein P, Hivelin M. Face transplant: longterm follow-up and results of a prospective open study. Lancet 2016;388:1398-1407. (https://www.ncbi.nlm.nih.gov/pubmed/27567680)

     

    Pasmant E, Gilbert-Dussardier B, Petit A, de Laval B, Luscan A, Gruber A, Lapillonne H, Deswarte C, Goussard P, Laurendeau I, Uzan B, Pflumio F, Brizard F, Vabres P, Naguibvena I, Fasola S, Millot F, Porteu F, Vidaud D, Landman-Parker J, Ballerini P. SPRED1, a RAS MAPK pathway inhibitor that causes Legius syndrome, is a tumour suppressor downregulated in paediatric acute myeloblastic leukaemia. Oncogene 2015;34:631-8. (https://www.ncbi.nlm.nih.gov/pubmed/24469042)

     

    De Raedt T, Beert E*, Pasmant E*, Luscan A, Brems H, Ortonne N, Helin K, Hornick JL, Mautner V, Kehrer-Sawatzki H, Clapp W, Bradner J, Vidaud M, Upadhyaya M, Legius E, Cichowski K. PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature 2014;514:247-51. *equal contribution (https://www.ncbi.nlm.nih.gov/pubmed/25119042)

     

    Luscan A, Shackleford G, Masliah-Planchon J, Laurendeau I, Ortonne N, Varin J, Lallemand F, Leroy K, Dumaine V, Hivelin M, Borderie D, De Raedt T, Valeyrie-Allanore L, Larousserie F, Terris B, Lantieri L, Vidaud M, Vidaud D, Wolkenstein P, Parfait B, Bieche I, Massaad C, Pasmant E. The activation of the WNT signaling pathway is a Hallmark in neurofibromatosis type 1 tumorigenesis. Clin Cancer Res. 2014;20:358-71. (https://www.ncbi.nlm.nih.gov/pubmed/24218515)

     

     

    Team’s news

    • Team members are involved in the development and management of the NGS platform shared between the Cochin hospital and the Institut Cochin. The current Cochin NGS Platform launched in March 2012. The first NGS sequencer was acquired thanks to research funds (CAP NF Foundation). In 2013, a tripartite operating agreement was signed between Paris Descartes University, AP-HP, and INSERM. In 2014, the NGS Platform was labelled by the Paris Descartes University.
    • Béatrice Parfait is the Manager of the cell bank (CRB) of the Cochin hospital
    • The team is actively participating to the French and European NF network that organized the first global NF meeting in Paris in 2018 (600 participants) (http://www.nf-paris2018.com/)
    • Team members participate to regular teaching courses in: Pharmacy (DGFSP2, DGFSP3, DU NGS), Medicine (DGFSM2, DGFSM3), Science (L2, L3, M1, M2) faculties
    • Michel Vidaud is director of the Doctoral Institute of the Paris Descartes University, (http://ecolesdoctorales.parisdescartes.fr/)
    • Funding by The Gilbert Family Foundation's Gene Therapy Initiative (https://www.prnewswire.com/news-releases/gilbert-family-foundation-announces-12-million-gene-therapy-initiative-to-address-underlying-cause-of-nf1-300764288.html)
    • The team benefits from recurrent financial supports the CAP NF Foundation (https://www.anrfrance.fr/page/123995-fondation-cap-nf)