Networks

• Institut Carnot pour la recherche partenariale dans le domaine du LYMphome (CALYM)
• Cancéropôle Nord-Ouest
• Développement de la génomique médicale à l’ère post-exome « Génomique » (FHU-G4 GENOMIQUE)

Participation à des consortia internationaux : Alzheimer Disease European Sequencing (coPI), ERN Genturis, International Cancer and Cognition Task Force (ICCTF), COST ERNEST action, i-GPCRnet IRN, etc.

Nombreux réseaux nationaux et adossement à des centres de référence : Association nationale des praticiens de génétique moléculaire (ANPGM), Groupe Génétique et Cancer, Centre National de Référence Malades Alzheimer Jeunes (CNRMAJ), Centre de Référence Maladies Rares anomalies du développement et syndromes malformatifs, Laboratoires de biologie médicale de référence (formes familiales de maladie d’Alzheimer, calcifications cérébrales primaires, déficience intellectuelle, amyotrophie spinale infantile, diagnostic moléculaire du syndrome de Li-Fraumeni, diagnostic moléculaire des prédispositions héréditaires au cancer colorectal), Plan France Médecine Génomique 2025, GIS autisme et TND, Blood and Brain institute, Réseau PériNat, ANOCEF (Onco-neurotox et Gopa), etc.

  Research Topics

• Development of new methods for detection and interpretation of genetic alterations
• Alteration of gene dosage
• RNA diseases
• Genetics of colorectal cancer and Li-Fraumeni syndrome
• Targeted therapies in colorectal cancer
• Genetics and physiopathology of Alzheimer and dementia
• Genetic bases of psychoses

  Composition

• 29 teacher-researchers and researchers
• 12 technicians / engineers
• 2 postdoctoral researchers
• 8 graduate / undergraduate students

  Facilities

• Genomic facilities : CGH-array, new generation sequencing bioinformatics, splicing assay platform
• L2 laboratory for retroviral infection
• Transgenic drosophila laboratory
• Expression of human proteins in yeast

  Activity

The Inserm U1245, composed of 2 teams “Cancer genetics” and “Neurogenetics”, is focused on the study of hereditary predisposition to colorectal cancer and pediatric tumours, somatic genetics and targeted therapies of colorectal cancer, genetics and physiopathology of dementias and RNA diseases (splicing and microARNs). The projects are based on national recruitment of patients and strong interactions with many French and European groups. The unit has a strong commitment in the translational research and technological transfer with the development of new methods to detect and interpret genetic variations.

  Main contributions

•  Development of the QMPSF method allowing routine detection of germline and somatic quantitative genomic alterations
• Development of ex vivo splicing assays allowing to reclassify unclassified genetic variations as splicing mutations
• Characterisation of the molecular bases of hereditary non polyposis colorectal cancer and of the genetic predisposition to childhood cancers
• Identification of molecular markers of resistance or sensitivity to targeted therapies in colorectal cancer
• Detection of the APP duplication in Alzheimer disease
• Identification by genetic screen in Drosophila of modifiers of tau-induced neurotoxicity
• Role of hyperprolinemia in psychoses and mental retardation
• Role of gene dosage variation in psychoses and mental retardation
• Development in collaboration with the Interactive Biosftware company of the Alamut software suite for the analysis of nucleotide variations

  Latest publications

2014

• Castéra L, Krieger S, Rousselin A, Legros A, Baumann JJ, Bruet O, Brault B, Fouillet R, Goardon N, Letac O, Baert-Desurmont S, Tinat J, Bera O, Dugast C, Berthet P, Polycarpe F, Layet V, Hardouin A, Frébourg T and Vaur D. Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes. Eur J Hum Genet 2014: doi: 10.1038.
  24549055
• Frebourg T. The challenge for the next generation of medical geneticists. Hum Mutat 2014, 35: 909-11.
  24838402
• Tournier I, Marlin R, Walton K, Charbonnier F, Coutant S, Théry JC, Charbonnier C, Spurrell C, Vezain M, Ippolito L, Bougeard G, Roman H, Tinat J, Sabourin JC, Stoppa-Lyonnet D, Caron O, Bressac-de Paillerets B, Vaur D, King MC, Harrison C and Frebourg T. Germline Mutations of Inhibins in Early-Onset Ovarian Epithelial Tumors. Hum Mutat 2014, 35: 294-7.
  24302632

2013

• Nicolas G1, Pottier C, Maltête D, Coutant S, Rovelet-Lecrux A, Legallic S, Rousseau S, Vaschalde Y, Guyant-Maréchal L, Augustin J, Martinaud O, Defebvre L, Krystkowiak P, Pariente J, Clanet M, Labauge P, Ayrignac X, Lefaucheur R, Le Ber I, Frébourg T, Hannequin D and Campion D. Mutation of the PDGFRB gene as a cause of idiopathic basal ganglia calcification. Neurology 2013, 80: 181-7.
  23255827
• Zerdoumi Y1, Aury-Landas J, Bonaïti-Pellié C, Derambure C, Sesboüé R, Renaux-Petel M, Frebourg T, Bougeard G and Flaman JM. Drastic effect of germline TP53 missense mutations in Li-Fraumeni patients. Hum Mutat 2013, 34: 453-61.
  23172776

2012

• Pottier C, Hannequin D, Coutant S, Rovelet-Lecrux A, Wallon D, Rousseau S, Legallic S, Paquet C, Bombois S, Pariente J, Thomas-Anterion C, Michon A, Croisile B, Etcharry-Bouyx F, Berr C, Dartigues JF, Amouyel P, Dauchel H, Boutoleau-Bretonnière C, Thau. High frequency of potentially pathogenic SORL1 mutations in autosomal dominant early-onset Alzheimer disease. Mol Psychiatry 2012, 17: 875-9.
  22472873

2011

• Houlle S, Charbonnier F, Houivet E, Tinat J, Buisine MP, Caron O, Benichou J, Baert-Desurmont S and Frebourg T. Evaluation of Lynch syndrome modifier genes in 748 MMR mutation carriers. Eur J Hum Genet 2011, 19: 887-92.
  21407259

2009

• Carelle-Calmels N, Saugier-Veber P, Girard-Lemaire F, Rudolf G, Doray B, Guérin E, Kuhn P, Arrivé M, Gilch C, Schmitt E, Fehrenbach S, Schnebelen A, Frébourg T and Flori E. Genetic compensation in a human genomic disorder. N Engl J Med 2009, 360: 1211-6.
  19297573

2008

• Bougeard G, Sesboüé R, Baert-Desurmont S, Vasseur S, Martin C, Tinat J, Brugières L, Chompret A, de Paillerets BB, Stoppa-Lyonnet D, Bonaïti-Pellié C and Frébourg T; French LFS working group. Molecular basis of the Li-Fraumeni syndrome: an update from the French LFS families. J Med Genet 2008, 45: 535-8.
  18511570

2006

• Rovelet-Lecrux A, Hannequin D, Raux G, Le Meur N, Laquerrière A, Vital A, Dumanchin C, Feuillette S, Brice A, Vercelletto M, Dubas F, Frebourg T and Campion D. APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. Nat Genet 2006, 38: 24-6.
  16369530