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

• Published in: International journal of cancer 2002-08, Vol.100 (6), p.669-677
• Main Authors: Behrends, Uta, Jandl, Thomas, Golbeck, Anja, Lechner, Brigitte, Müller‐Weihrich, Stephan, Schmid, Irene, Till, Holger, Berthold, Frank, Voltz, Raymond, Mautner, Josef M.
• Format: Article
• Language: English
• Subjects: Adult; Amino Acid Sequence; Base Sequence; Biological and medical sciences; 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; Hu syndrome; Humans; Intermediate Filament Proteins; Medical sciences; Models, Genetic; Molecular Sequence Data; Nerve Tissue Proteins - genetics; neuroblastoma; Neuroblastoma - genetics; Neurology; Nuclear Proteins - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; RNA-Binding Proteins - genetics; Sequence Homology, Amino Acid; SEREX; Time Factors; tumor antigen; tumor marker; Tumors of the nervous system. Phacomatoses
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.10550

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 α‐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, HuD1proc). 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. © 2002 Wiley‐Liss, Inc.