Composition

• 11 researchers, engineers and technicians
• 4 PhD students, 2 master II students

  Facilities

• Conventional cytogenetics, molecular cytogenetics
• Molecular biology, PCR, quantitative PCR, sequencing, cloning
• BeadExpress Reader (Illumina)
• Cytometry (FC 500 BeckMan Coulter)
• Sequencer (Applied 3130 Genetic Analyser, Applied 310)
• Quantitative PCR (Applied 7900, 7500 Fast)
• Pyrosequencing (Qiagen)
• Annexes: cold room
• Haematology department (150 new lymphoma cases per year, Agreement for haematopoietic stem cell transplants)
• Clinical research unit   
• Pathology department and  tissue bank (DNA/RNA extraction from frozen or FFPE tissues, Immunohistochemistry, Tissue-Micro-array)

  Activity

Our team is a monothematic team that ensures a real cooperation between all structures and all members. It is comprised of:

• A genetic laboratory, the competence of which in the lymphoma field is widely recognized. Its technical abilities range from conventional and molecular cytogenetics to genomics and expression analysis. Its technical resources have been upgraded over the past three years and now offer new perspectives in both the fundamental and the translational domains, as for biomarkers validation.
• A department of clinical hematology specialized in the management of lymphoma patients, with a recruitment of about 150 new patients a year, allowing the collect of tumoral samples. This department works in close collaboration with a clinical research unit, which insures a real time actualization of clinical annotations. This collaboration make it also possible to identify and validate biomarkers pertinent for the management of non Hodgkin lymphoma patients by using samples and clinical data issued from multicenter trials.
• A pathology laboratory which analyses dispends and stores NHL samples, in conjunction with a regional repository. To date, more than 1000 lymphoma frozen samples are available. This laboratory developed a network to collect all lymphoma samples at the regional level. It is able to perform DNA or RNA extraction, FISH analysis and to prepare tissue micro arrays.

Two major axes are developed:

• The first focused on the fundamental aspects of lymphomagenesis. Its major goals were the clarification of the transformation pathways associated to the deregulation of major oncogenes, including BCL6, and the evaluation of the importance of the microenvironment for the proliferation of the tumoral cells. We particularly focused on genes coding for the immunoglobulin chains of the B-cell receptor (variable and switch regions), which allowed us to contribute to a better understanding of their fundamental roles during lymphomagenesis.
• The second axe focused on the evaluation of the impact of recurrent genetic abnormalities on the phenotype and on the clinical behaviour of lymphoid B-cell tumors. Among others goals, we aimed to transfer fundamental aspects of the molecular events occurring during the development of these tumors to develop new tests predictive of the diagnosis and the prognosis of mature B-cell proliferations.

  Main contributions

• Identification of the BCL6 gene involved in more than 30% of aggressive B-cell lymphomas
• Assessment of the prognosis value of recurrent genetic abnormalities in follicular lymphomas and diffuse large B-cell lymphomas in the setting of international clinical trials
• Identification of biomarkers related to response to targeted therapy in lymphomas

  Latest publications

2012

• Couronné L, Ruminy P, Waultier-Rascalou A, Rainville V, Cornic M, Picquenot JM, Figeac M, Bastard C, Tilly H and Jardin F. Mutation mismatch repair genes deletions in diffuse large B-cell lymphoma. Leuk Lymphoma 2012
  23066952
• Guney S, Jardin F, Bertrand P, Mareschal S, Parmentier F, Picquenot JM, Tilly H and Bastard C. Several mechanisms lead to the inactivation of the CDKN2A (P16), P14ARF, or CDKN2B (P15) genes in the GCB and ABC molecular DLBCL subtypes. Genes Chromosomes Cancer 2012, 51: 858-67.
  22619049
• Jardin F and Tilly H. Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone: until what age. Leuk Lymphoma 2012, 53: 521-2.
  22335535
• Lanic H, Mareschal S, Mechken F, Picquenot JM, Cornic M, Maingonnat C, Bertrand P, Clatot F, Bohers E, Stamatoullas A, Leprêtre S, Rainville V, Ruminy P, Bastard C, Tilly H, Becker S, Vera P and Jardin F. Interim positron emission tomography scan associated with international prognostic index and germinal center B cell-like signature as prognostic index in diffuse large B-cell lymphoma. Leuk Lymphoma 2012, 53: 34-42.
  21806349
• Launay E, Pangault C, Bertrand P, Jardin F, Lamy T, Tilly H, Tarte K, Bastard C and Fest T. High rate of TNFRSF14 gene alterations related to 1p36 region in de novo follicular lymphoma and impact on prognosis. Leukemia 2012, 26: 559-62.
  21941365
• Sibon D, Fournier M, Brière J, Lamant L, Haioun C, Coiffier B, Bologna S, Morel P, Gabarre J, Hermine O, Sonet A, Gisselbrecht C, Delsol G, Gaulard P and Tilly H. Long-Term Outcome of Adults With Systemic Anaplastic Large-Cell Lymphoma Treated Within the Groupe d'Etude des Lymphomes de l'Adulte Trials. J Clin Oncol 2012
  23045585
• Tilly H, Morschhauser F, Salles G, Casasnovas RO, Feugier P, Molina TJ, Jardin F, Terriou L, Haioun C and Coiffier B. Phase 1b study of lenalidomide in combination with rituximab-CHOP (R2-CHOP) in patients with B-cell lymphoma. Leukemia 2012
  22733106

2011

• Guney S, Bertrand P, Jardin F, Ruminy P, Kerckaert JP, Tilly H and Bastard C. Molecular characterization of 9p21 deletions shows a minimal common deleted region removing CDKN2A exon 1 and CDKN2B exon 2 in diffuse large B-cell lymphomas. Genes Chromosomes Cancer 2011, 50: 715-25.
  21638516
• Jardin F, Ruminy P, Parmentier F, Troussard X, Vaida I, Stamatoullas A, Leprêtre S, Penther D, Duval AB, Picquenot JM, Courville P, Capiod JC, Tilly H, Bastard C and Marolleau JP. TET2 and TP53 mutations are frequently observed in blastic plasmacytoid dendritic cell neoplasm. Br J Haematol 2011, 153: 413-6.
  21275969
• Mareschal S, Lanic H, Ruminy P, Bastard C, Tilly H and Jardin F. The proportion of activated B-cell like subtype among de novo diffuse large B-cell lymphoma increases with age. Haematologica 2011, 96: 1888-90.
  21859735
• Peyrade F, Jardin F, Thieblemont C, Thyss A, Emile JF, Castaigne S, Coiffier B, Haioun C, Bologna S, Fitoussi O, Lepeu G, Fruchart C, Bordessoule D, Blanc M, Delarue R, Janvier M, Salles B, André M, Fournier M, Gaulard P and Tilly H; Groupe d'Etude. Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial. Lancet Oncol 2011, 12: 460-8.
  21482186
• Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G and Ti. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet 2011, 378: 1858-67.
  22118442
• Ruminy P, Etancelin P, Couronné L, Parmentier F, Rainville V, Mareschal S, Bohers E, Burgot C, Cornic M, Bertrand P, Lenormand B, Picquenot JM, Jardin F, Tilly H and Bastard C. The isotype of the BCR as a surrogate for the GCB and ABC molecular subtypes in diffuse large B-cell lymphoma. Leukemia 2011, 25: 681-8.
  21233831
• Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet 2011, 377: 42-51.
  21176949

2010

• Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Fermé C and Tilly H. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood 2010, 116: 2040-5.
  20548096
• Jardin F, Jais JP, Molina TJ, Parmentier F, Picquenot JM, Ruminy P, Tilly H, Bastard C, Salles GA, Feugier P, Thieblemont C, Gisselbrecht C, de Reynies A, Coiffier B, Haioun C and Leroy K. Diffuse large B-cell lymphomas with CDKN2A deletion have a distinct gene expression signature and a poor prognosis under R-CHOP treatment: a GELA study. Blood 2010, 116: 1092-104.
  20435884
• Tilly H and Dreyling M; ESMO Guidelines Working Group. Diffuse large B-cell non-Hodgkin's lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010, 21: v172-4.
  20555073

2009

• Jardin F, Callanan M, Penther D, Ruminy P, Troussard X, Kerckaert JP, Figeac M, Parmentier F, Rainville V, Vaida I, Bertrand P, Duval AB, Picquenot JM, Chaperot L, Marolleau JP, Plumas J, Tilly H and Bastard C. Recurrent genomic aberrations combined with deletions of various tumour suppressor genes may deregulate the G1/S transition in CD4+CD56+ haematodermic neoplasms and contribute to the aggressiveness of the disease. Leukemia 2009, 23: 698-707.
  19158833
• Jardin F, Picquenot JM, Parmentier F, Ruminy P, Cornic M, Penther D, Bertrand P, Lanic H, Cassuto O, Humbrecht C, Lemasle E, Wautier A, Bastard C and Tilly H. Detection of gene copy number aberrations in mantle cell lymphoma by a single quantitative multiplex PCR assay: clinicopathological relevance and prognosis value. Br J Haematol 2009, 146: 607-18.
  19594747

2008

• Coiffier B and Tilly H. Dose dance in lymphomas. Lancet Oncol 2008, 9: 84-6.
  18237844
• Jardin F, Ruminy P, Kerckaert JP, Parmentier F, Picquenot JM, Quief S, Villenet C, Buchonnet G, Tosi M, Frebourg T, Bastard C and Tilly H. Detection of somatic quantitative genetic alterations by multiplex polymerase chain reaction for the prediction of outcome in diffuse large B-cell lymphomas. Haematologica 2008, 93: 543-50.
  18287131
• Ruminy P, Jardin F, Picquenot JM, Parmentier F, Contentin N, Buchonnet G, Tison S, Rainville V, Tilly H and Bastard C. S(mu) mutation patterns suggest different progression pathways in follicular lymphoma: early direct or late from FL progenitor cells. Blood 2008, 112: 1951-9.
  18515657

2007

• Bertrand P, Bastard C, Maingonnat C, Jardin F, Maisonneuve C, Courel MN, Ruminy P, Picquenot JM and Tilly H. Mapping of MYC breakpoints in 8q24 rearrangements involving non-immunoglobulin partners in B-cell lymphomas. Leukemia 2007, 21: 515-23.
  17230227
• Jardin F, Ruminy P, Bastard C and Tilly H. The BCL6 proto-oncogene: a leading role during germinal center development and lymphomagenesis. Pathol Biol (Paris) 2007, 55: 73-83.
  16815642
• Ruminy P, Jardin F, Penther D, Picquenot JM, Parmentier F, Buchonnet G, Bertrand P, Tilly H and Bastard C. Recurrent disruption of the Imu splice donor site in t(14;18) positive lymphomas: a potential molecular basis for aberrant downstream class switch recombination. Genes Chromosomes Cancer 2007, 46: 735-44.
  17455255

2006

• Jardin F, Sahota SS, Ruminy P, Parmentier F, Picquenot JM, Rainville V, Buchonnet G, Leprêtre S, Tilly H and Bastard C. Novel Ig V gene features of t(14;18) and t(3;14) de novo diffuse large B-cell lymphoma displaying germinal center-B cell like and non-germinal center-B cell like markers. Leukemia 2006, 20: 2070-4.
  16990787
• Ruminy P, Jardin F, Picquenot JM, Gaulard P, Parmentier F, Buchonnet G, Maisonneuve C, Tilly H and Bastard C. Two patterns of chromosomal breakpoint locations on the immunoglobulin heavy-chain locus in B-cell lymphomas with t(3;14)(q27;q32): relevance to histology. Oncogene 2006, 25: 4947-54.
  16619046