A novel diffuse large B-cell lymphoma-associated cancer testis antigen encoding a PAS domain protein.
Here we report that the OX-TES-1 SEREX antigen, which showed immunological reactivity with serum from four out of 10 diffuse large B-cell lymphoma (DLBCL) patients, is encoded by a novel gene, PAS domain containing 1 (PASD1). PASD1_v1 cDNA encodes a 639 amino-acid (aa) protein product, while an alternatively spliced variant (PASD1_v2), lacking intron 14, encodes a 773 aa protein, the first 638 aa of which are common to both proteins. The PASD1-predicted protein contains a PAS domain that, together with a putative leucine zipper and nuclear localisation signal, suggests it encodes a transcription factor. The expression of PASD1_v1 mRNA was confirmed by RT-PCR in seven DLBCL-derived cell lines, while PASD1_v2 mRNA appears to be preferentially expressed in cell lines derived from non-germinal centre DLBCL. Immunophenotyping studies of de novo DLBCL patients' tumours with antibodies to CD10, BCL-6 and MUM1 indicated that two patients mounting an immune response to PASD1 were of a poor prognosis non-germinal centre subtype. Expression of PASD1 mRNA was restricted to normal testis, while frequent expression was observed in solid tumours (25 out of 68), thus fulfilling the criteria for a novel cancer testis antigen. PASD1 has potential for lymphoma vaccine development that may also be widely applicable to other tumour types.
Liggins
A P
AP
Nuffield Department of Clinical Laboratory Sciences, University of Oxford, LRF Immunodiagnostics Unit, Level 4 Academic Block, John Radcliffe Hospital, Oxford, Oxfordshire OX3 9DU, UK. amanda.liggins@ndcls.ox.ac.uk
Brown
P J
PJ
Asker
K
K
Pulford
K
K
Banham
A H
AH
D000595:Amino Acid Sequence; D000917:Antibody Formation; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology; D019496:Cancer Vaccines; D018076:DNA, Complementary; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D016393:Lymphoma, B-Cell / Q000276:immunology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000276:immunology
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018076:DNA, Complementary; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C403097:SPANXC protein, human; C116037:PAS domain kinases; D017346:Protein Serine-Threonine Kinases