title: Primary cutaneous follicle center lymphoma and primary cutaneous large B-cell lymphoma, leg type, are both targeted by aberrant somatic hypermutation but demonstrate differential expression of AID.
abstract: We assessed primary cutaneous large B-cell lymphoma, leg type (PCLBCL, leg type; n = 13), and primary cutaneous follicle center lymphoma (PCFCL; n = 19) for somatic hypermutation (SHM) of BCL6, and aberrant SHM of MYC, RhoH/TTF, and PAX5. We demonstrate SHM of BCL6 in 8 PCLBCLs (62%), leg type, and 7 PCFCL patients (37%), and aberrant SHM in PAX5, RhoH/TTF, and/or MYC in 7 PCLBCLs (54%), leg type, and 10 PCFCL patients (53%). The majority of mutations consisted of single base-pair substitutions (n = 54) with rare deletions/insertions (n = 4), and displayed molecular features typical of the SHM process. Quantitative real-time PCR and immunohistochemical stainings for activation-induced cytidine deaminase, which is indispensable for SHM, demonstrated significantly higher expression in PCLBCL, leg type. Our results suggest that (aberrant) SHM may contribute to the pathogenesis of PCLBCL, leg type, and PCFCL and is not restricted to diffuse large B-cell lymphomas with an aggressive clinical behavior.
authors.affiliation: Department of Dermatology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Remco
authors.initials: R
authors.lastname: Dijkman
authors.forename: Cornelis P
authors.initials: CP
authors.lastname: Tensen
authors.forename: Maike
authors.initials: M
authors.lastname: Buettner
authors.forename: Gerald
authors.initials: G
authors.lastname: Niedobitek
authors.forename: Rein
authors.initials: R
authors.lastname: Willemze
authors.forename: Maarten H
authors.initials: MH
authors.lastname: Vermeer
mesh_terms: D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007866:Leg / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008224:Lymphoma, Follicular / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D017354:Point Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D009363:Neoplasm Proteins; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D043525:Cytosine Deaminase; D003564:Cytidine Deaminase