Abstract
Aberrant expression of microRNAs is widely accepted to be pathogenetically involved in nodal diffuse large B-cell lymphomas (DLBCLs). However, the microRNAs profiles of primary cutaneous large B-cell lymphomas (PCLBCLs) are not yet described. Its two main subtypes, i.e., primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) and primary cutaneous follicle center lymphoma (PCFCL) are characterized by an activated B-cell (ABC)-genotype and a germinal center B-cell (GCB)-genotype, respectively. We performed high-throughput sequencing analysis on frozen tumor biopsies from 19 cases of PCFCL and PCLBCL-LT to establish microRNA profiles. Cluster analysis of the complete microRNome could not distinguish between the two subtypes, but 16 single microRNAs were found to be differentially expressed. Single microRNA RT-qPCR was conducted on formalin-fixed paraffin-embedded tumor biopsies of 20 additional cases, confirming higher expression of miR-9-5p, miR-31-5p, miR-129-2-3p and miR-214-3p in PCFCL as compared to PCLBCL-LT. MicroRNAs previously described to be higher expressed in ABC-type as compared to GCB-type nodal DLBCL were not differentially expressed between PCFCL and PCLBCL-LT. In conclusion, PCFCL and PCLBCL-LT differ in their microRNA profiles. In contrast to their gene expression profile, they only show slight resemblance with the microRNA profiles found in GCB- and ABC-type nodal DLBCL.
Highlights
Primary cutaneous large B-cell lymphomas (PCLBCLs) are a group of malignant lymphoproliferative disorders presenting in the skin with no evidence of extracutaneous disease at the time of diagnosis [1]
primary cutaneous follicle center lymphoma (PCFCL) and PCLBCL-LT have gene expression profiles corresponding to germinal center B-cell (GCB)-type diffuse large B-cell lymphoma (DLBCL) and activated B-cell (ABC)-type nodal diffuse large B-cell lymphomas (DLBCLs), respectively [5]
The complete microRNomes of PCLBCL-LT and PCFCL did not allow their separation by unsupervised hierarchical clustering, and PCLBCL-LT did not cluster together with activated B-cells, its postulated normal counterpart (Figure S1 in File S2)
Summary
Primary cutaneous large B-cell lymphomas (PCLBCLs) are a group of malignant lymphoproliferative disorders presenting in the skin with no evidence of extracutaneous disease at the time of diagnosis [1]. In the latest World Health Organization (WHO) 2008 classification two main types of PCLBCL are distinguished: primary cutaneous follicle center lymphoma (PCFCL) and primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) [2]. 95%), whereas PCLBCL-LT has a more aggressive clinical course (5 year OS approximately 40%) [3]. PCFCL and PCLBCL-LT have gene expression profiles corresponding to germinal center B-cell (GCB)-type diffuse large B-cell lymphoma (DLBCL) and activated B-cell (ABC)-type nodal DLBCL, respectively [5]. Clinical distinction at the time of first diagnosis between these different subtypes of PCLBCL is important, as the first choice of treatment differs between the two entities. PCFCL can be adequately treated with radiotherapy, but the more aggressive behavior of PCLBCL-LT warrants for treatment with anthracyclin-based chemotherapy combined with rituximab [6]
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