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Chapter 76 Origin of Non-Hodgkin Lymphoma 1233

ABC DLBCL GCB DLBCL PMBL

IRF4
PIM2
CCND2
FOXP1
CD44
IGHM
PRKCB1
PDE4B
MME
CR2
KCNN3
BCL6
LRMP
LMO2
MYBL1
SLAMF1
SERPINA9
GCET2
TNFRSF8
CCL17
JAK2
PDCD1LG2
CD274
TRAF1
IL4I1
MAL

Lymphoma biopsies

Fold
relative
expression 0.25x 0.5x 1x 2x 4x
Fig. 76.3 GENES CHARACTERISTICALLY EXPRESSED BY SUBGROUPS OF DIFFUSE LARGE
B-CELL LYMPHOMA (DLBCL). Activated B-cell–like (ABC) DLBCL, germinal center B cell–like (GCB)
DLBCL, and primary mediastinal B-cell lymphoma (PMBL). Each column represents gene expression data
from a single DLBCL biopsy sample, and each row represents expression of a single gene. Relative gene
expression is indicated according to the color scale shown. (From Alizadeh, AA: Distinct types of diffuse large B-cell
lymphoma identified by gene expression profiling. Nature 403:503, 2000.)

TABLE Frequency of Recurrent Genetic Aberrations in Diffuse Large B-Cell Lymphoma Subtypes
76.1
Genetic Feature ABC DLBCL GCB DLBCL PMBL Notes
BCL2 translocation t(14;18) 0% 40%–50% 20% Alternatively translocated to light chain
loci 5–10% of time
BCL2 amplification 34% 10% 16%
BCL6 translocation t(3;V) 25% 10% 20% Variable translocation partners (14q32,
(q27;V) 2p11, 22q11, 4p11, 6p21, 11q23)
3q amplification 25% 0% <5%
9q24 amplification 5% 0% 45%
PRDM1/PRDM1 deletion/ 25% 0% Unknown
mutation
REL amplification 0 15% 25%
Recurrent mutation CARD11, MYD88, CD79B EZH2, GNA13, BCL2 PTPN1, SOCS1, STAT6
MYC rearrangement t(8;14) 5%–10% of all DLBCLs 25%–30% occur with
(q24;q32) t(14;18)(q32;q21)
ABC, Activated B cell–like; DLCBL, diffuse large B-cell lymphoma; GCB, germinal center B cell–like;mPMBL, primary mediastinal B-cell lymphoma
Compiled from Iqbal J: Distinctive patterns of BCL6 molecular alterations and their functional consequences in different subgroups of diffuse large B-cell lymphoma.
Leukemia 21:2332, 2007; Iqbal J, Neppalli VT, Wright G, et al: BCL2 expression is a prognostic marker for the activated B cell–like type of diffuse large B-cell lymphoma.
J Clin Oncol 24:961, 2006; Iqbal J, Weisenburger DD, Greiner TC, et al: Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in
angioimmunoblastic T-cell lymphoma. Blood 115:1026, 2010; Pasqualucci L. Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphoma. J Exp Med
203:311, 2006; and Tam W: Mutational analysis of PRDM1 indicates a tumor-suppressor role in diffuse large B-cell lymphomas. Blood 107:4090, 2006.