BCL-6 is essential for germinal center formation and thus for affinity matu
ration of immunoglobulin (Ig) genes by somatic mutations. The 5'-noncoding
region of the BCL-6 gene is even a target for the mutation machinery. Trans
locations of the BCL-6 gene to heterologous promoters and mutations of its
5'-noncoding regulatory region were reported to be potential mechanisms for
deregulating BCL-6 expression and for playing a role in the genesis of non
-Hodgkin lymphoma. In line with this hypothesis is the observation that B-c
ell lymphoma with somatic mutations, such as diffuse large B-cell lymphoma
and follicular lymphoma, also carry BCL-6 mutations, some of which are recu
rrently detectable. Classic Hodgkin disease (cHD) is also derived from B ce
lls with high loads of somatic mutations and thus a further candidate for B
CL-6 mutations. To determine the presence and potential role of BCL-6 mutat
ions in cHD, the 5'-noncoding BCL-6 proportion of single Hodgkin and Reed-S
ternberg (HRS) cells from 6 cases of cHD and 6 cases of HD-derived cell lin
es was analyzed. All B-cell-derived Ho cases and cell lines harbored BCL-6
mutations. In contrast, both T-cell-derived HD cases and cell lines were de
void of BCL-6 mutations. With only one exception, there were no lymphoma-sp
ecific recurrent BCL-6 mutations detected, and BCL-6 protein was absent fro
m the HRS cells of most cases. In conclusion, (1) somatic BCL-6 mutations a
re restricted to cHD cases of B-cell origin, and (2) the BCL-6 mutations re
present mostly irrelevant somatic base substitutions without consequences f
or BCL-6 protein expression and the pathogenesis of cHD. (Blood, 2001;97:24
01-2405) (C) 2001 by The American Society of Hematology.