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Novel products of the HUD , HUC , NNP‐1 and α‐internexin genes identified by autologous antibody screening of a pediatric neuroblastoma library
Author(s) -
Behrends Uta,
Jandl Thomas,
Golbeck Anja,
Lechner Brigitte,
MüllerWeihrich Stephan,
Schmid Irene,
Till Holger,
Berthold Frank,
Voltz Raymond,
Mautner Josef M.
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10550
Subject(s) - neuroblastoma , antigen , antibody , biology , untranslated region , gene , serology , immunology , tumor antigen , microbiology and biotechnology , messenger rna , immunotherapy , genetics , immune system , cell culture
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, 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. © 2002 Wiley‐Liss, Inc.