CD44 activation in mature B-cell malignancies by a novel recurrent IGH translocation.
Using inverse polymerase chain reaction, we identified CD44, located on chromosome 11p13, as a novel translocation partner of IGH in 9 of 114 cases of gastric, nongastric extranodal, follicular, and nodal diffuse large B-cell lymphoma (DLBCL). Notably, these translocations involving IGHSmu were detected in follicular lymphomas and exclusively in germinal center B cell-ike (GCB)-DLBCLs. CD44 is not expressed in reactive GC B cells. The IGHSmu/CD44 translocations substitute Smu for the CD44 promoter and remove exon 1 of CD44, resulting in the overexpression of Imu-CD44 hybrid mRNA transcripts activated from derivative 11 that encode a new CD44 variant lacking the leader peptide and with a unique C-terminus (CD44DeltaEx1). When overexpressed in vitro in the CD44(-) GCB-DLBCL cell line BJAB, CD44DeltaEx1-green fluorescent protein localized to the cytoplasm and nucleus, whereas CD44s-green fluorescent protein (standard form) localized to the plasma membrane. The ectopic expression of CD44DeltaEx1 in BJAB cells enhanced their proliferation rate and clonogenic ability, indicating a possible pathogenic role of the translocation.
Hu
Xiao-Tong
XT
Department of Pathology, University of Hong Kong, Queen Mary Hospital, Hong Kong.
Chen
Yun-Wen
YW
Liang
Anthony C T
AC
Au
Wing-Yan
WY
Wong
Kai-Yau
KY
Wan
Thomas S K
TS
Wong
Michelle L Y
ML
Shen
Lijun
L
Chan
Ka-Kui
KK
Guo
Tianhuan
T
Chu
Kent-Man
KM
Tao
Qian
Q
Chim
Chor-Sang
CS
Loong
Florence
F
Choi
William W L
WW
Lu
Liwei
L
So
Chi-Chiu
CC
Chan
Li Chong
LC
Kwong
Yok-Lam
YL
Liang
Raymond H S
RH
Srivastava
Gopesh
G
D045744:Cell Line, Tumor; D056905:Chromosome Breakpoints; D002880:Chromosomes, Human, Pair 11; D002883:Chromosomes, Human, Pair 14; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014178:Translocation, Genetic
C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D007143:Immunoglobulin Heavy Chains; D049452:Green Fluorescent Proteins