title: VH mutation status and VDJ rearrangement structure in mantle cell lymphoma: correlation with genomic aberrations, clinical characteristics, and outcome.
abstract: Immunoglobulin variable heavy chain gene (VH) mutation status and VDJ rearrangement structure were analyzed in 141 patients with mantle cell lymphoma (MCL) and correlated with biologic and clinical characteristics; 29% of the MCLs displayed mutated VH using a 98% germline homology cutoff. Striking differences occurred in the VH mutation subgroups with respect to the use of specific V genes. Rearrangements involving V4-34 and V3-21 were almost exclusively unmutated, whereas rearrangements using V4-59 and V3-23 were typically mutated. Significant association occurred between mutated VH with shorter CDR3 lengths and the use of JH4b. V3-21 and V4-59 were involved in highly characteristic rearrangements, implying that antigen specificity might have been involved in MCL development. There was no evidence for isotype switch recombination or Bcl-6 expression in any MCL. ZAP70 expression was not different in VH-mutated or -unmutated MCL. Although the deletions 11q- and 17p- showed a balanced distribution, an overrepresentation was observed for trisomies +3q, +8q, and tetraploidy in the VH-unmutated subgroup and +12q in the VH-mutated subgroup. Clinically, mutated VH was associated with a higher rate of complete remission, but there was no correlation between VH mutation status and other clinical characteristics or overall survival.
authors.affiliation: Department of Internal Medicine III, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Kienle
authors.forename: Alexander
authors.initials: A
authors.lastname: Kröber
authors.forename: Tiemo
authors.initials: T
authors.lastname: Katzenberger
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: Elke
authors.initials: E
authors.lastname: Leupolt
authors.forename: Thomas F E
authors.initials: TF
authors.lastname: Barth
authors.forename: Peter
authors.initials: P
authors.lastname: Möller
authors.forename: Axel
authors.initials: A
authors.lastname: Benner
authors.forename: Annett
authors.initials: A
authors.lastname: Habermann
authors.forename: Hans Konrad
authors.initials: HK
authors.lastname: Müller-Hermelink
authors.forename: Martin
authors.initials: M
authors.lastname: Bentz
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.forename: Hartmut
authors.initials: H
authors.lastname: Dōhner
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
mesh_terms: D002869:Chromosome Aberrations; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000276:immunology*; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D013997:Time Factors; D016896:Treatment Outcome; D014314:Trisomy; D045567:VDJ Recombinases / Q000378:metabolism*
chemical_list: D007143:Immunoglobulin Heavy Chains; D045567:VDJ Recombinases