VH mutation status and VDJ rearrangement structure in mantle cell lymphoma: correlation with genomic aberrations, clinical characteristics, and outcome.
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.
Kienle
Dirk
D
Department of Internal Medicine III, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm, Germany.
Kröber
Alexander
A
Katzenberger
Tiemo
T
Ott
German
G
Leupolt
Elke
E
Barth
Thomas F E
TF
Möller
Peter
P
Benner
Axel
A
Habermann
Annett
A
Müller-Hermelink
Hans Konrad
HK
Bentz
Martin
M
Lichter
Peter
P
Dōhner
Hartmut
H
Stilgenbauer
Stephan
S
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*
D007143:Immunoglobulin Heavy Chains; D045567:VDJ Recombinases