Novel t(5;9)(q33;q22) fuses ITK to SYK in unspecified peripheral T-cell lymphoma

• Published in: Leukemia Vol. 20; no. 2; pp. 313 - 318
• Main Authors: Streubel, B, Vinatzer, U, Willheim, M, Raderer, M, Chott, A
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.02.2006
• Subjects: Aged; Aged, 80 and over; Anaplastic large-cell lymphoma; Bcl-6 protein; Breakpoints; CD3 antigen; CD4 antigen; CD5 antigen; Chromosome translocations; Chromosomes; Chromosomes, Human, Pair 5 - genetics; Chromosomes, Human, Pair 9 - genetics; Classification; Cloning; Cloning, Molecular; Cytogenetic Analysis; Domains; Female; Follicles; Homology; Humans; Immunohistochemistry; Immunophenotyping; In Situ Hybridization, Fluorescence; Intracellular Signaling Peptides and Proteins - genetics; Itk protein; Kinases; Leukemia; Lymphatic system; Lymphocytes T; Lymphoma; Lymphoma, Non-Hodgkin - genetics; Lymphoma, Non-Hodgkin - pathology; Lymphoma, T-Cell, Peripheral - genetics; Lymphoma, T-Cell, Peripheral - pathology; Male; Middle Aged; Oncogene Proteins, Fusion - genetics; Pleckstrin; Proline; Protein-tyrosine kinase; Protein-Tyrosine Kinases - genetics; Reverse Transcriptase Polymerase Chain Reaction; Subgroups; Syk Kinase; Syk protein; T-cell lymphoma; T-Lymphocytes - immunology; T-Lymphocytes - pathology; Transcription, Genetic; Translocation; Translocation, Genetic; Tyrosine; United States > US; Austria
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2404045

Among peripheral T-cell lymphomas (PTCL), the heterogeneous category of unspecified PTCL represents the most common subtype. Nevertheless, recurrent chromosomal translocations are unknown in this aggressive type of lymphoma. Here we describe a novel t(5;9)(q33;q22) in unspecified PTCL. Molecular analyses delineated the breakpoints to ITK and SYK resulting in a previously undescribed expression of the Syk tyrosine kinase by Itk. ITK-SYK transcripts were detected in five of 30 (17%) unspecified PTCL, but not in cases of angioimmunoblastic T-cell lymphoma (n=9) and anaplastic lymphoma kinase-negative anaplastic large-cell lymphoma (n=7). In all five translocation-positive cases, the breakpoints were identical fusing the N-terminal pleckstrin homology domain and proline-rich region of ITK to the tyrosine kinase domain of SYK. Three of the five t(5;9)(q33;q22)+ unspecified PTCL shared a very similar histological pattern with predominant involvement of lymphoid follicles and the same CD3+CD5+CD4+bcl-6+CD10+ immunophenotype. These results demonstrate the presence of a recurrent t(5;9)(q33;q22) in a subset of unspecified PTCL, which may represent a novel distinct subgroup of PTCL.