title: MYD88 L265P Mutations, But No Other Variants, Identify a Subpopulation of DLBCL Patients of Activated B-cell Origin, Extranodal Involvement, and Poor Outcome.
abstract: Mutations in MYD88 are found in different lymphoproliferative disorders associated with particular biologic characteristics and clinical impact. The aim of this study was to analyze the incidence of MYD88 mutations and its clinical impact in diffuse large B-cell lymphoma (DLBCL).
  
  
  
  The incidence, clinicobiological features, and outcome of 213 patients (115 M/98 F; median age, 65 years) with DLBCL treated with immunochemotherapy in a single institution according to MYD88 mutational status as assessed by an allele-specific PCR assay were analyzed. The cell of origin (COO) was determined in 129 cases by gene expression.
  
  
  
  MYD88 mutations were found in 47 cases (22%), including L265P in 39 and S219C and M232F in 4 cases, respectively. Patients with MYD88 L265P were older, presenting frequent extranodal involvement, and mostly corresponded to activated B-cell like (ABC) subtype, whereas no preference in COO was observed in patients with other MYD88 mutations. Five-year overall survival (OS) for MYD88 wild-type, MYD88 L265P, and other variants was 62%, 52%, and 75%, respectively (P = 0.05). International Prognostic Index (IPI) (HR, 2.71; P < 0.001) and MYD88 L265P (HR, 1.786; P = 0.023) were independent variables predicting OS in the multivariate analysis. However, MYD88 L265P lost its independent value when COO was included in the model.
  
  
  
  Our findings indicate that MYD88 L265P mutations, but no other variants, identify a subgroup of DLBCL mainly of ABC origin, with extranodal involvement and poor outcome. Clin Cancer Res; 22(11); 2755-64. ©2016 AACR.
authors.affiliation: Hematology Department, Hospital Clínic, IDIBAPS, Barcelona, Spain.
authors.forename: Jordina
authors.initials: J
authors.lastname: Rovira
authors.affiliation: Pathology Department, Hospital Clínic, IDIBAPS, Barcelona, Spain.
authors.forename: Kennosuke
authors.initials: K
authors.lastname: Karube
authors.affiliation: Pathology Department, Hospital Clínic, IDIBAPS, Barcelona, Spain.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Valera
authors.affiliation: Pathology Department, Hospital Clínic, IDIBAPS, Barcelona, Spain.
authors.forename: Dolors
authors.initials: D
authors.lastname: Colomer
authors.affiliation: Genomics Unit, Hospital Clínic, IDIBAPS, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Enjuanes
authors.affiliation: Pathology Department, Hospital Clínic, IDIBAPS, Barcelona, Spain.
authors.forename: Lluís
authors.initials: L
authors.lastname: Colomo
authors.affiliation: Hematology Department, Hospital Clínic, IDIBAPS, Barcelona, Spain.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Martínez-Trillos
authors.affiliation: Hematology Department, Hospital Clínic, IDIBAPS, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Giné
authors.affiliation: Hematology Department, Hospital Clínic, IDIBAPS, Barcelona, Spain.
authors.forename: Ivan
authors.initials: I
authors.lastname: Dlouhy
authors.affiliation: Hematology Department, Hospital Clínic, IDIBAPS, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Magnano
authors.affiliation: Hematology Department, Hospital Clínic, IDIBAPS, Barcelona, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Delgado
authors.affiliation: Pathology Department, Hospital Clínic, IDIBAPS, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Martínez
authors.affiliation: Pathology Department, Hospital Clínic, IDIBAPS, Barcelona, Spain.
authors.forename: Neus
authors.initials: N
authors.lastname: Villamor
authors.affiliation: Pathology Department, Hospital Clínic, IDIBAPS, Barcelona, Spain. Universitat Barcelona, Barcelona, Spain.
authors.forename: Elías
authors.initials: E
authors.lastname: Campo
authors.affiliation: Hematology Department, Hospital Clínic, IDIBAPS, Barcelona, Spain. alopezg@clinic.ub.es.
authors.forename: Armando
authors.initials: A
authors.lastname: López-Guillermo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008213:Lymphocyte Activation; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88