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

Authors

  • Uta Behrends,

    Corresponding author
    1. Kinderklinik, Hämatologie-Onkologie, Technische Universität, München, Germany
    2. Klinische Kooperationsgruppe Pädiatrische Tumorimmunologie, GSF-Institut für Klinische Molekularbiologie und Tumorgenetik, Forschungszentrum für Umwelt und Gesundheit, München, Germany
    • Kinderklinik der Technischen Universität München, Kölner Platz 1, 80804 Munich, Germany
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    • Fax: +49-89-3068-3811

  • Thomas Jandl,

    1. Kinderklinik, Hämatologie-Onkologie, Technische Universität, München, Germany
    2. Klinische Kooperationsgruppe Pädiatrische Tumorimmunologie, GSF-Institut für Klinische Molekularbiologie und Tumorgenetik, Forschungszentrum für Umwelt und Gesundheit, München, Germany
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  • Anja Golbeck,

    1. Kinderklinik, Hämatologie-Onkologie, Technische Universität, München, Germany
    2. Klinische Kooperationsgruppe Pädiatrische Tumorimmunologie, GSF-Institut für Klinische Molekularbiologie und Tumorgenetik, Forschungszentrum für Umwelt und Gesundheit, München, Germany
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  • Brigitte Lechner,

    1. Kinderklinik, Hämatologie-Onkologie, Technische Universität, München, Germany
    2. Klinische Kooperationsgruppe Pädiatrische Tumorimmunologie, GSF-Institut für Klinische Molekularbiologie und Tumorgenetik, Forschungszentrum für Umwelt und Gesundheit, München, Germany
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  • Stephan Müller-Weihrich,

    1. Kinderklinik, Hämatologie-Onkologie, Technische Universität, München, Germany
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  • Irene Schmid,

    1. Dr. von Haunersches Kinderspital, Ludwig-Maximilians-Universität, München, Germany
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  • Holger Till,

    1. Dr. von Haunersches Kinderspital, Ludwig-Maximilians-Universität, München, Germany
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  • Frank Berthold,

    1. Zentrum für Pädiatrische Hämatologie und Onkologie, Universität, Köln, Germany
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  • Raymond Voltz,

    1. Institut für Klinische Neuroimmunologie, Ludwig-Maximilians-Universität, München, Germany
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  • Josef M. Mautner

    1. Kinderklinik, Hämatologie-Onkologie, Technische Universität, München, Germany
    2. Klinische Kooperationsgruppe Pädiatrische Tumorimmunologie, GSF-Institut für Klinische Molekularbiologie und Tumorgenetik, Forschungszentrum für Umwelt und Gesundheit, München, Germany
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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 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.

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