title: BCL2 mutations do not confer adverse prognosis in follicular lymphoma patients treated with rituximab.
abstract: BCL2 mutations have been suggested to confer an adverse prognosis to follicular lymphoma (FL) patients, but their prognostic value has not been assessed in patients treated with a rituximab-containing regimen. Here we evaluated the prognostic value of BCL2 mutations in a large prospective cohort of 252 patients with FL treated with immunochemotherapy in the PRIMA randomized trial. Using a DNA-targeted sequencing approach, we detected amino acid altering mutations in 135 patients (54%) and showed that these mutations were probably mediated by the over-activation of AICDA (activation-induced cytidine deaminase) in the context of the t(14;18) translocation. The BCL2 variants identified in PRIMA patients affected the BH1, BH2, and BH3 functional motifs at a lower frequency than the N-terminus and flexible loop domain, with mostly conservative aminoacid changes. With a median follow-up of 6.7 years, we did not observe any impact of BCL2 mutations either on overall survival or progression-free survival.
authors.affiliation: Service d'hématologie biologique, Hospices Civils de Lyon, 69495, Pierre Bénite cedex, France.|INSERM1052, CNRS 5286, Université Claude Bernard, Faculté de Médecine Lyon-Sud Charles Mérieux, Université de Lyon, 69495, Pierre Bénite cedex, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Huet
authors.affiliation: Genentech, South San Francisco, California.
authors.forename: Edith
authors.initials: E
authors.lastname: Szafer-Glusman
authors.affiliation: Institut Carnot CALYM, Pierre Bénite, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Tesson
authors.affiliation: Aix-Marseille University and Institut Paoli-Calmettes, Marseille, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Xerri
authors.affiliation: Genentech, South San Francisco, California.
authors.forename: Wayne J
authors.initials: WJ
authors.lastname: Fairbrother
authors.affiliation: Genentech, South San Francisco, California.
authors.forename: Kiran
authors.initials: K
authors.lastname: Mukhyala
authors.affiliation: Genentech, South San Francisco, California.
authors.forename: Chris
authors.initials: C
authors.lastname: Bolen
authors.affiliation: Genentech, South San Francisco, California.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Punnoose
authors.affiliation: Synergie Lyon Cancer, Plateforme de bioinformatique 'Gilles Thomas', Centre Léon Bérard, Lyon, France.
authors.forename: Laurie
authors.initials: L
authors.lastname: Tonon
authors.affiliation: Department of Pathology, Centre Léon Bérard, Lyon, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Chassagne-Clément
authors.affiliation: Department of Hematology, Nancy University Hospital, Nancy, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Feugier
authors.affiliation: Synergie Lyon Cancer, Plateforme de bioinformatique 'Gilles Thomas', Centre Léon Bérard, Lyon, France.|Equipe Erable, INRIA Grenoble-Rhône-Alpes, Montbonnot-Saint Martin, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Viari
authors.affiliation: Department of Hematology, Henri Becquerel Comprehensive Cancer Center and Normandie Univ, UNIROUEN, Inserm U1245, Team "Genomics and biomarkers in lymphoma and solid tumors", Rouen, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Jardin
authors.affiliation: INSERM1052, CNRS 5286, Université Claude Bernard, Faculté de Médecine Lyon-Sud Charles Mérieux, Université de Lyon, 69495, Pierre Bénite cedex, France.|Service d'hématologie clinique, Hospices Civils de Lyon, 69495 Pierre Bénite cedex, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
authors.affiliation: Service d'hématologie biologique, Hospices Civils de Lyon, 69495, Pierre Bénite cedex, France.|INSERM1052, CNRS 5286, Université Claude Bernard, Faculté de Médecine Lyon-Sud Charles Mérieux, Université de Lyon, 69495, Pierre Bénite cedex, France.
authors.forename: Pierre
authors.identifier: http://orcid.org/0000-0003-1724-4792
authors.initials: P
authors.lastname: Sujobert
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D009154:Mutation; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D000069283:Rituximab / Q000627:therapeutic use; D014178:Translocation, Genetic; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D000069283:Rituximab