Identification and characterization of peripheral T-cell lymphoma-associated SEREX antigens

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article numbere23916
JournalPLoS One
Volume6
Issue number8
DOIs
Publication statusPublished - 22 Aug 2011
Externally publishedYes

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Peripheral T-Cell Lymphoma
T-cells
lymphoma
T-lymphocytes
antigens
Antigens
B-Cell Lymphoma
Cells
Serum
Gene Library
B-lymphocytes
Anaplastic Large-Cell Lymphoma
T-Lymphocytes
Cell Line
Proteins
T-Cell Lymphoma
Neoplasm Antigens
Hodgkin Disease
pathogenesis
Non-Hodgkin's Lymphoma

Cite this

Cooper, C. D. O., Lawrie, C. H., Liggins, A. P., Collins, G. P., Hatton, C. S. R., Pulford, K., & Banham, A. H. (2011). Identification and characterization of peripheral T-cell lymphoma-associated SEREX antigens. PLoS One, 6(8), [e23916]. https://doi.org/10.1371/journal.pone.0023916
Cooper, Christopher D O ; Lawrie, Charles H. ; Liggins, Amanda P. ; Collins, Graham P. ; Hatton, Christian S R ; Pulford, Karen ; Banham, Alison H. / Identification and characterization of peripheral T-cell lymphoma-associated SEREX antigens. In: PLoS One. 2011 ; Vol. 6, No. 8.
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Cooper, CDO, Lawrie, CH, Liggins, AP, Collins, GP, Hatton, CSR, Pulford, K & Banham, AH 2011, 'Identification and characterization of peripheral T-cell lymphoma-associated SEREX antigens', PLoS One, vol. 6, no. 8, e23916. https://doi.org/10.1371/journal.pone.0023916

Identification and characterization of peripheral T-cell lymphoma-associated SEREX antigens. / Cooper, Christopher D O; Lawrie, Charles H.; Liggins, Amanda P.; Collins, Graham P.; Hatton, Christian S R; Pulford, Karen; Banham, Alison H.

In: PLoS One, Vol. 6, No. 8, e23916, 22.08.2011.

Research output: Contribution to journalArticle

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T1 - Identification and characterization of peripheral T-cell lymphoma-associated SEREX antigens

AU - Cooper, Christopher D O

AU - Lawrie, Charles H.

AU - Liggins, Amanda P.

AU - Collins, Graham P.

AU - Hatton, Christian S R

AU - Pulford, Karen

AU - Banham, Alison H.

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AB - 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.

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