Identification and Characterization of Peripheral T-Cell Lymphoma-Associated SEREX Antigens

Christopher D O Cooper,Charles H Lawrie,Alison H Banham,Graham P Collins,Karen Pulford,Amanda P Liggins,Christian S R Hatton,John D Minna

doi:10.1371/journal.pone.0023916

Christopher D O Cooper, Charles H Lawrie + Show 6 more

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https://doi.org/10.1371/journal.pone.0023916

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Journal: PLoS ONE	Publication Date: Aug 22, 2011
Citations: 11	License type: CC BY 4.0

Affiliation: University of Oxford, John Radcliffe Hospital, Biodonostia

Abstract

Peripheral T-cell lymphomas (PTCL) are generally less common and pursue a more aggressive clinical course than B-cell lymphomas, with the T-cell phenotype itself being a poor prognostic factor in adult non-Hodgkin lymphoma (NHL). With notable exceptions such as ALK+ anaplastic large cell lymphoma (ALCL, ALK+), the molecular abnormalities in PTCL remain poorly characterised. We had previously identified circulating antibodies to ALK in patients with ALCL, ALK+. Thus, as a strategy to identify potential antigens associated with the pathogenesis of PTCL, not otherwise specified (PTCL, NOS), we screened a testis cDNA library with sera from four PTCL, NOS patients using the SEREX (serological analysis of recombinant cDNA expression libraries) technique. We identified nine PTCL, NOS-associated antigens whose immunological reactivity was further investigated using sera from 52 B- and T-cell lymphoma patients and 17 normal controls. The centrosomal protein CEP250 was specifically recognised by patients sera and showed increased protein expression in cell lines derived from T-cell versus B-cell malignancies. TCEB3, BECN1, and two previously uncharacterised proteins, c14orf93 and ZBTB44, were preferentially recognised by patients' sera. Transcripts for all nine genes were identified in 39 cancer cell lines and the five genes encoding preferentially lymphoma-recognised antigens were widely expressed in normal tissues and mononuclear cell subsets. In summary, this study identifies novel molecules that are immunologically recognised in vivo by patients with PTCL, NOS. Future studies are needed to determine whether these tumor antigens play a role in the pathogenesis of PTCL.

Highlights

Peripheral T-cell lymphomas (PTCL) are relatively uncommon, and together with NK-cell neoplasms, comprise approximately 12% of all non-Hodgkin lymphomas (NHL) [1]
Three antigens, ODF2, CEP110 and CEP250, are centrosomal proteins while four antigens, TCEB3, RBPJ, RIF1 and ZBTB44, have roles associated with transcription
Using the SEREX technique we have identified nine antigens that are immunologically recognised by autoantibodies from patients with PTCL, NOS

Summary

Introduction

Peripheral T-cell lymphomas (PTCL) are relatively uncommon, and together with NK-cell neoplasms, comprise approximately 12% of all non-Hodgkin lymphomas (NHL) [1]. Because of the lack of consistent immunophenotypic and genetic markers, approximately 30% of these tumours are classified into a category described as ‘‘not otherwise specified’’ (PTCL, NOS) in the current World Health Organisation classification scheme [2]. In Western countries nodal tumours are the most common form and include three main subtypes: PTCL, NOS, angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-positive (ALCL, ALK+) [3]. PTCL generally express T-cell associated markers, with nodal tumours most often being CD4+ and extranodal cases being CD8+. The molecular abnormalities underlying PTCL are generally poorly understood, and in contrast to data from patients with BNHL, reports are relatively rare. The notable exception is ALCL, ALK+ which express a variety of oncogenic ALK fusion proteins [6,7] and are routinely identified as a specific entity using an anti-ALK monoclonal antibody (ALK1) [8]

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