title: Analysis of VH genes in marginal zone lymphoma reveals marked heterogeneity between splenic and nodal tumors and suggests the existence of clonal selection.
abstract: OBJECTIVE
  To clarify the relationship between splenic (SMZL) and nodal marginal zone (NMZL) lymphomas, we analyzed immunoglobulin variable heavy chain (VH) gene usage and mutation patterns in these tumors.
  
  
  METHODS
  VH genes were cloned and sequenced from 49 lymphoma samples (35 SMZL and 14 NMZL).
  
  
  RESULTS
  A biased usage of VH gene was found with overrepresentation of VH1 in SMZL cases (13/35) and VH4 in NMZL cases (7/14). Evidence for antigen driven mutations was identified in 8 SMZL and 4 NMZL cases. Three cases out of 18 with clones analyzed from spleen and peripheral blood demonstrated intra-clonal diversity, with evidence of clonal selection in one case, indicating the possibility of antigen-driven clonal expansion. Eleven SMZL cases (31%) but only 2 NMZL (14%) cases were unmutated. No differences in clinical outcome and overall survival were found between the unmutated and mutated cases.
  
  
  CONCLUSIONS
  The pattern of somatic mutation and the VH gene segment usage appear to differ between SMZL and NMZL, suggesting that these are distinct pathological entities. Moreover, a biased usage of certain sequences suggests that tumor cells in SMZL may be subjected to antigen selection.
authors.affiliation: Equipe Accueil 3737 Pathologie des Cellules Lymphoïdes, Université Claude Bernard, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Traverse-Glehen
authors.forename: Frédéric
authors.initials: F
authors.lastname: Davi
authors.forename: Elsa
authors.initials: E
authors.lastname: Ben Simon
authors.forename: Evelyne
authors.initials: E
authors.lastname: Callet-Bauchu
authors.forename: Pascale
authors.initials: P
authors.lastname: Felman
authors.forename: Lucile
authors.initials: L
authors.lastname: Baseggio
authors.forename: Sophie
authors.initials: S
authors.lastname: Gazzo
authors.forename: Catherine
authors.initials: C
authors.lastname: Thieblemont
authors.forename: Carole
authors.initials: C
authors.lastname: Charlot
authors.forename: Bertrand
authors.initials: B
authors.lastname: Coiffier
authors.forename: Françoise
authors.initials: F
authors.lastname: Berger
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017635:Clonal Anergy / Q000235:genetics; D005260:Female; D005803:Genes, Immunoglobulin / Q000502:physiology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008206:Lymphatic Diseases / Q000097:blood / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D013160:Splenic Neoplasms / Q000097:blood / Q000235:genetics*
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region