Submitted August 25, 2005
Accepted February 11, 2006
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
Remco Dijkman, Cornelis P Tensen, Maike Buettner, Gerald Niedobitek, Rein Willemze, and Maarten H Vermeer*
Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands
Institute of Pathology, Friedrich-Alexander-University, Erlangen, Germany
* Corresponding author; email: M.H.Vermeer{at}lumc.nl.
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 c-MYC, RhoH/TTF and PAX5. We demonstrate SHM of BCL6 in 8 (62%) PCLBCL, leg type and 7 (37%) PCFCL patients and aberrant SHM in PAX-5, RhoH/TTF, and/or c-MYC in 7 (54%) PCLBCL, leg type and 10 (53%) PCFCL patients. 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.
