Novel products of the HUD, HUC, NNP-1 and alpha-internexin genes identified by autologous antibody screening of a pediatric neuroblastoma library

Int J Cancer. 2002 Aug 20;100(6):669-77. doi: 10.1002/ijc.10550.

Abstract

Autologous serological screening of a cDNA expression library (SEREX) derived from childhood neuroblastoma led to the identification of 10 different antigens, including 6 novel gene products. The novel antigen 018INX was derived from a small open reading frame in a region of alpha-internexin mRNA that was previously described as 3' untranslated region. 018INX thus represents a novel type of tumor antigen. Five novel gene products were derived from NNP-1 (NNP3) and Hu genes (HuC-L, HuD3, HuDY, HuD1pro(c)). As indicated by sequence analysis, these antigens were generated by alternative splicing and/or alternative promoter usage or allelic polymorphism. mRNA expression analyses revealed different tissue restrictions of novel compared to known HuD and NNP-1 transcripts in normal and malignant tissues. The expressions patterns of distinct transcripts indicated potential clinical meanings as diagnostic and/or prognostic tissue markers. When kinetics of serum antibody titres against SEREX-defined antigens were compared to tumor load over time in our patient with neuroblastoma, we found 100-fold increases of anti-Hu and anti-018INX antibody titres preceding the clinical diagnosis of recurrent tumor growth after 2 years. When sera of pediatric patients with cancer (30) and healthy controls (30) were tested for humoral responses to SEREX-defined neuroblastoma antigens, we detected antibodies against all known antigens and NNP3 with low frequencies and titres in control sera, while anti-018INX and anti-Hu antibodies were found in cancer patients only. Our findings indicate that SEREX-defined tumor antigens might provide novel tools for understanding and treatment of this aggressive childhood malignancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Blotting, Southern
  • Carrier Proteins / genetics*
  • Case-Control Studies
  • Child, Preschool
  • DNA, Complementary / metabolism
  • ELAV Proteins
  • ELAV-Like Protein 3
  • ELAV-Like Protein 4
  • Female
  • Gene Library
  • Humans
  • Intermediate Filament Proteins
  • Models, Genetic
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics*
  • Neuroblastoma / genetics*
  • Nuclear Proteins / genetics*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Time Factors

Substances

  • Carrier Proteins
  • DNA, Complementary
  • ELAV Proteins
  • ELAV-Like Protein 3
  • ELAV-Like Protein 4
  • ELAVL3 protein, human
  • ELAVL4 protein, human
  • Intermediate Filament Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • RRP1 protein, human
  • alpha-internexin