ABSTRACT
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)-a subtype of Hodgkin lymphoma (HL)-is characterized by a low content of tumor cells, the lymphocyte predominant (LP) cells. Transformation into diffuse large B-cell lymphoma (DLBCL) occurs in about 10% of patients. We performed whole-genome mutation analysis of the DLBCL components from two composite lymphomas consisting of clonally related NLPHL and DLBCL as a means to identify candidate tumor suppressor genes and oncogenes in NLPHL. The analysis of LP cells for selected mutations of the DLBCL revealed that most mutations are also present in the LP cells, indicating a close relationship between the two components. The analysis of 62 selected genes in NLPHL by targeted ultra-deep sequencing revealed three novel highly recurrently mutated genes (each mutated in ~50% of cases), that is, DUSP2, SGK1 and JUNB. SGK1 was expressed in the LP cells of primary NLPHL cases and in the NLPHL cell line DEV. Administration of an SGK1 inhibitor induced apoptosis in the NLPHL cell line DEV and the DLBCL cell line Farage, suggesting a pathogenetic role of SGK1 in the LP and DLBCL cells. In summary, the present study identifies SGK1, DUSP2 and JUNB as novel key players in the pathogenesis of NLPHL.
Subject(s)
Dual Specificity Phosphatase 2/genetics , Hodgkin Disease/genetics , Immediate-Early Proteins/genetics , Mutation/genetics , Protein Serine-Threonine Kinases/genetics , Transcription Factors/genetics , Adult , DNA Mutational Analysis , High-Throughput Nucleotide Sequencing , Hodgkin Disease/pathology , Humans , Immunophenotyping , Lymph Nodes/metabolism , Lymph Nodes/pathology , Lymphocytes/metabolism , Lymphocytes/pathology , Lymphoma, Follicular/genetics , Lymphoma, Follicular/pathology , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Neoplasm Staging , PrognosisABSTRACT
The authors discuss their experience with the ulnar artery forearm island flap in 54 cases of hand surgery. They discuss its advantages over the radial island forearm flap and examine further technical possibilities in hand reconstruction, such as the compound flap. Although these reconstructive techniques do not have any sequelae, they involve the sacrifice of a major artery and should thus be used only in complex cases with very clear indications and as a last resort.
