Analysis of VH genes in marginal zone lymphoma reveals marked heterogeneity between splenic and nodal tumors and suggests the existence of clonal selection.
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.
Traverse-Glehen
Alexandra
A
Equipe Accueil 3737 Pathologie des Cellules Lymphoïdes, Université Claude Bernard, France.
Davi
Frédéric
F
Ben Simon
Elsa
E
Callet-Bauchu
Evelyne
E
Felman
Pascale
P
Baseggio
Lucile
L
Gazzo
Sophie
S
Thieblemont
Catherine
C
Charlot
Carole
C
Coiffier
Bertrand
B
Berger
Françoise
F
Salles
Gilles
G
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*
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region