Novel products of the HUD, HUC, NNP-1 and alpha-internexin genes identified by autologous antibody screening of a pediatric neuroblastoma library.
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.
Behrends
Uta
U
Hämatologie-Onkologie, Kinderklinik der Technische Universität München, Kölner Platz 1, 80804 Munich, Germany. utabehrends@yahoo.de
Jandl
Thomas
T
Golbeck
Anja
A
Lechner
Brigitte
B
Müller-Weihrich
Stephan
S
Schmid
Irene
I
Till
Holger
H
Berthold
Frank
F
Voltz
Raymond
R
Mautner
Josef M
JM
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002675:Child, Preschool; D018076:DNA, Complementary / Q000378:metabolism; D051959:ELAV Proteins; D000067778:ELAV-Like Protein 3; D000067779:ELAV-Like Protein 4; D005260:Female; D015723:Gene Library; D006801:Humans; D007381:Intermediate Filament Proteins; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013997:Time Factors
D002352:Carrier Proteins; D018076:DNA, Complementary; D051959:ELAV Proteins; D000067778:ELAV-Like Protein 3; D000067779:ELAV-Like Protein 4; C490264:ELAVL3 protein, human; C498010:ELAVL4 protein, human; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C107468:RRP1 protein, human; C046643:alpha-internexin