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

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.

• Authors: Uta Behrends, Thomas Jandl, Anja Golbeck, Brigitte Lechner, Stephan Müller-Weihrich, Irene Schmid, Holger Till, Frank Berthold, Raymond Voltz, Josef M Mautner
• Journal: International journal of cancer (Int J Cancer) Vol. 100 Issue 6 Pg. 669-77 (Aug 20 2002) ISSN: 0020-7136 [Print] United States
• PMID: 12209604 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2002 Wiley-Liss, Inc.

Chemical References

• 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

Topics

• 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