RNASET2--an autoantigen in anaplastic large cell lymphoma identified by protein array analysis.
Characterising tumour-associated antigens (TAAs) not only represents an important approach to the identification of new diagnostic/prognostic markers, but can also provide information on disease processes and additional potential therapeutic targets. Preliminary screening of a protein macroarray, containing more than 12,000 different proteins, with sera from anaplastic lymphoma kinase (ALK)-negative and ALK-positive anaplastic large cell lymphoma (ALCL) patients identified ribonuclease and tumour suppressor protein Ribonuclease T2 (RNASET2), phosphatase lipid phosphate phosphatase-related protein type 3 (LPPR3) and apoptotic adaptor molecule Fas-associating protein (FADD) as ALK-negative ALCL-associated TAAs. Further validation of these observations was confirmed using the ALCL sera in reverse ELISAs. The circulating anti-RNASET2 autoantibodies present in ALCL patients' sera also recognised eukaryotically expressed RNASET2 protein. RNASET2 expression was then investigated in normal tissues and in lymphomas to explore its clinical potential. RNASET2 protein and mRNA levels showed highest expression in the spleen, leucocytes and pancreas. RNASET2 protein expression was not restricted to ALK-negative ALCL (81%), being expressed in ALK-positive ALCL (65%) as well as in a number of other lymphomas. The immunological recognition of RNASET2, its expression in ALCL and other lymphomas together with its known tumourigenic properties suggest that further studies on this autoantigen are warranted.
Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, UK.
Suketu
S
Patel
Hong
H
Chen
Laura
L
Monti
Edith
E
Gould
Eugenia
E
Haralambieva
Jasmin
J
Schmid
David
D
Toomey
Wilhelm
W
Woessmann
Giovanna
G
Roncador
Chris S R
CS
Hatton
Amanda P
AP
Liggins
Roberto
R
Taramelli
Alison H
AH
Banham
Francesco
F
Acquati
Derek
D
Murphy
Karen
K
Pulford
D000818:Animals; D001324:Autoantigens / Q000032:analysis / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D017728:Lymphoma, Large-Cell, Anaplastic / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D040081:Protein Array Analysis; D012260:Ribonucleases / Q000032:analysis / Q000378:metabolism* / Q000502:physiology*; D014018:Tissue Distribution; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000378:metabolism* / Q000502:physiology*; D054928:Validation Studies as Topic
D001324:Autoantigens; D025521:Tumor Suppressor Proteins; D012260:Ribonucleases; C425232:RNASET2 protein, human