Diffuse large B-cell lymphoma (DLBCL) is a common type of non-Hodgkin's lym
phoma (NHL) that is highly heterogeneous from both clinical and histopathol
ogic viewpoints. The immunoglobulin (Ig) heavy (H) chain variable region ge
nes were examined in 71 patients with untreated primary DLBCL, Fifty-eight
potentially functional V-H genes were detected in 53 DLBCL cases; V-H genes
were nonfunctional in 9 cases and were not detected in an additional 9 cas
es. The use of V-H gene families by DLBCL tumors was unbiased without overr
epresentation of any particular V-H gene or gene family. Analysis of Ig mut
ations in comparison to the most closely related germline gene disclosed mu
tated V-H genes in all but 1 DLBCL case. More than 2% difference from the m
ost similar germline sequence was detected in 52 potentially functional and
the 8 nonfunctional V-H gene sequences, whereas less than 2% difference fr
om the germline sequence was observed in 3 V-H gene isolates. Only 3 V-H ge
ne isolates were unmutated, No correlation was found between V-H gene use,
mutation level, and International Prognostic Index (IPI) or survival, Six o
f 8 tested tumors showed evidence of ongoing somatic mutations. Evidence fo
r positive or negative antigen selection pressure was observed in 65% of mu
tated DLBCL cases. Our findings indicate that the etiology and the driving
forces for clonal expansion are heterogeneous, which may explain the well-k
nown clinical and pathologic heterogeneity of DLBCL, (C) 2000 by The Americ
an Society of Hematology.