A novel diffuse large B-cell lymphoma-associated cancer testis antigen encoding a PAS domain protein

Br J Cancer. 2004 Jul 5;91(1):141-9. doi: 10.1038/sj.bjc.6601875.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibody Formation
  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / immunology
  • Cancer Vaccines
  • DNA, Complementary
  • Gene Expression Profiling*
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • Lymphoma, B-Cell / immunology*
  • Lymphoma, Large B-Cell, Diffuse / immunology*
  • Male
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics*
  • Prognosis
  • Protein Serine-Threonine Kinases / genetics*
  • RNA, Messenger
  • Reverse Transcriptase Polymerase Chain Reaction
  • Testis / immunology

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • DNA, Complementary
  • Neoplasm Proteins
  • RNA, Messenger
  • SPANXC protein, human
  • PAS domain kinases
  • Protein Serine-Threonine Kinases