OBJECTIVES: Waldenstrom macroglobulinemia (WM) is a B-cell lymphoma characterized by the accumulation of lymphocytes and plasmacytic cells in the bone marrow and by excess production of immunoglobulin M in serum. WM has been closely linked with the MYD88(L265P) mutation. Whole genome sequencing has identified somatic mutations in the CXCR4 gene in ∼29% of WM cases with MYD88(L265P). CXCR4 mutations may interfere with treatment response to ibrutinib. The goal of this study was to design and validate a clinical assay to detect CXCR4 mutations. METHODS: Thirty-three low-grade B-cell lymphomas with plasmacytic differentiation (23 MYD88(L265P) and 10 MYD88(WT)) involving various samples types (fresh and formalin-fixed tissues) formed the study group. We designed and validated Sanger sequencing and pyrosequencing assays to detect mutations in CXCR4 in a Clinical Laboratory Improvement Amendments-approved clinical laboratory. RESULTS: We identified 8 cases with CXCR4 mutations, including 5 single nucleotide substitutions (3 resulting in p.S338* and 1 in p.R334*), and 3 insertion/deletions. Seven of 8 CXCR4 mutated cases were also MYD88(L265P) mutant. Among the single nucleotide substitutions, we identified a novel missense variant (p.L326P) and a previously reported variant (G335S) of uncertain clinical significance. CONCLUSIONS: We successfully validated a set of clinical assays to detect mutations in CXCR4 mutations in a clinical laboratory.
OBJECTIVES:Waldenstrom macroglobulinemia (WM) is a B-cell lymphoma characterized by the accumulation of lymphocytes and plasmacytic cells in the bone marrow and by excess production of immunoglobulin M in serum. WM has been closely linked with the MYD88(L265P) mutation. Whole genome sequencing has identified somatic mutations in the CXCR4 gene in ∼29% of WM cases with MYD88(L265P). CXCR4 mutations may interfere with treatment response to ibrutinib. The goal of this study was to design and validate a clinical assay to detect CXCR4 mutations. METHODS: Thirty-three low-grade B-cell lymphomas with plasmacytic differentiation (23 MYD88(L265P) and 10 MYD88(WT)) involving various samples types (fresh and formalin-fixed tissues) formed the study group. We designed and validated Sanger sequencing and pyrosequencing assays to detect mutations in CXCR4 in a Clinical Laboratory Improvement Amendments-approved clinical laboratory. RESULTS: We identified 8 cases with CXCR4 mutations, including 5 single nucleotide substitutions (3 resulting in p.S338* and 1 in p.R334*), and 3 insertion/deletions. Seven of 8 CXCR4 mutated cases were also MYD88(L265P) mutant. Among the single nucleotide substitutions, we identified a novel missense variant (p.L326P) and a previously reported variant (G335S) of uncertain clinical significance. CONCLUSIONS: We successfully validated a set of clinical assays to detect mutations in CXCR4 mutations in a clinical laboratory.
Authors: Ruben A L de Groen; Anne M R Schrader; Marie José Kersten; Steven T Pals; Joost S P Vermaat Journal: Haematologica Date: 2019-11-07 Impact factor: 9.941
Authors: Daniela Drandi; Philippe Decruyenaere; Martina Ferrante; Fritz Offner; Jo Vandesompele; Simone Ferrero Journal: Diagnostics (Basel) Date: 2022-04-12
Authors: Jorge J Castillo; Jithma P Abeykoon; Joshua N Gustine; Saurabh Zanwar; Kirsten Mein; Catherine A Flynn; Maria G Demos; Maria L Guerrera; Amanda Kofides; Xia Liu; Manit Munshi; Nickolas Tsakmaklis; Rebecca King; Guang Yang; Zachary R Hunter; Ranjana H Advani; Maria Lia Palomba; Stephen M Ansell; Morie A Gertz; Prashant Kapoor; Steven P Treon Journal: Br J Haematol Date: 2020-11-18 Impact factor: 6.998