Novel tumor antigens identified by autologous antibody screening of childhood medulloblastoma cDNA libraries.
Medulloblastoma is an embryonal childhood malignancy with poor prognosis. By screening 4 medulloblastoma cDNA expression libraries (SEREX) with autologous sera, 15 different antigens were identified. These antigens were encoded by 3 novel genes, genes of unknown function (KIAA0445, KIAA1853, KIAA0665, FLJ13942, HSPC213), a proto-oncogene (rab18), candidate tumor suppressor genes (BAP1, PRDM13) and genes encoding a motor protein (kinesin-2), a histone (H2A1.2), the ankyrin residue-rich nasopharyngeal cancer susceptibility protein (NZ16) and the transcription factor TZP, which is homologous to the tumor-associated antigens HCA58 and GLEA2. In a consecutive analysis of serum antibody titers and tumor load, a more than 10-fold increase in serum antibodies against PRDM13 preceded the clinical diagnosis of recurrent tumor growth in a patient with aggressive large cell medulloblastoma. When sera of pediatric patients with cancer (n = 40) and healthy controls (n = 40) were tested for humoral responses against the SEREX-defined antigens, 5 antigens were exclusively recognized by sera from cancer patients. These antigens included a novel rab18 gene product translated from mRNA sequences formerly described as 3' untranslated region. Humoral responses against 2 of the remaining 10 antigens were found preferentially in cancer patients. Antibodies against these antigens were detected in 8/40 and 12/40 cancer patients, respectively, but in only 1 healthy control. The 2 antigens were characterized by a tumor-specific deletion and a tumor-specific mutation, respectively. These findings indicate that the humoral immune response against medulloblastoma is directed against diverse antigens that may be useful as diagnostic markers or targets for immunotherapy.
Behrends
Uta
U
Kinderklinik, Hämatologie-Onkologie, Technische Universität, München, Germany. uta.behrends@yahoo.de
Schneider
Inken
I
Rössler
Sabine
S
Frauenknecht
Heinrich
H
Golbeck
Anja
A
Lechner
Brigitte
B
Eigenstetter
Gerhard
G
Zobywalski
Colette
C
Müller-Weihrich
Stephan
S
Graubner
Ulrike
U
Schmid
Irene
I
Sackerer
Dieter
D
Späth
Manfred
M
Goetz
Claudia
C
Prantl
Franz
F
Asmuss
Hans-Peter
HP
Bise
Karl
K
Mautner
Josef
J
D000293:Adolescent; D000595:Amino Acid Sequence; D000912:Antibodies, Neoplasm / Q000032:analysis*; D000951:Antigens, Neoplasm / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000276:immunology; D002675:Child, Preschool; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000276:immunology*; D004273:DNA, Neoplasm / Q000276:immunology; D015723:Gene Library; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007223:Infant; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D008527:Medulloblastoma / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D016036:Seroepidemiologic Studies; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D001323:Autoantibodies; D002135:Calcium-Binding Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D006657:Histones; C000715470:MAS1 protein, human; D009124:Muscle Proteins; D009687:Nuclear Proteins; D000090063:Proto-Oncogene Mas; C484168:RAB18 protein, human; D016601:RNA-Binding Proteins; C074632:STP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C074152:kinesin-II; D016547:Kinesins; D020691:rab GTP-Binding Proteins