title: CD44 activation in mature B-cell malignancies by a novel recurrent IGH translocation.
abstract: 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.
authors.affiliation: Department of Pathology, University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: Xiao-Tong
authors.initials: XT
authors.lastname: Hu
authors.forename: Yun-Wen
authors.initials: YW
authors.lastname: Chen
authors.forename: Anthony C T
authors.initials: AC
authors.lastname: Liang
authors.forename: Wing-Yan
authors.initials: WY
authors.lastname: Au
authors.forename: Kai-Yau
authors.initials: KY
authors.lastname: Wong
authors.forename: Thomas S K
authors.initials: TS
authors.lastname: Wan
authors.forename: Michelle L Y
authors.initials: ML
authors.lastname: Wong
authors.forename: Lijun
authors.initials: L
authors.lastname: Shen
authors.forename: Ka-Kui
authors.initials: KK
authors.lastname: Chan
authors.forename: Tianhuan
authors.initials: T
authors.lastname: Guo
authors.forename: Kent-Man
authors.initials: KM
authors.lastname: Chu
authors.forename: Qian
authors.initials: Q
authors.lastname: Tao
authors.forename: Chor-Sang
authors.initials: CS
authors.lastname: Chim
authors.forename: Florence
authors.initials: F
authors.lastname: Loong
authors.forename: William W L
authors.initials: WW
authors.lastname: Choi
authors.forename: Liwei
authors.initials: L
authors.lastname: Lu
authors.forename: Chi-Chiu
authors.initials: CC
authors.lastname: So
authors.forename: Li Chong
authors.initials: LC
authors.lastname: Chan
authors.forename: Yok-Lam
authors.initials: YL
authors.lastname: Kwong
authors.forename: Raymond H S
authors.initials: RH
authors.lastname: Liang
authors.forename: Gopesh
authors.initials: G
authors.lastname: Srivastava
mesh_terms: 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
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D007143:Immunoglobulin Heavy Chains; D049452:Green Fluorescent Proteins