title: Novel tumor antigens identified by autologous antibody screening of childhood medulloblastoma cDNA libraries.
abstract: 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.
authors.affiliation: Kinderklinik, Hämatologie-Onkologie, Technische Universität, München, Germany. uta.behrends@yahoo.de
authors.forename: Uta
authors.initials: U
authors.lastname: Behrends
authors.forename: Inken
authors.initials: I
authors.lastname: Schneider
authors.forename: Sabine
authors.initials: S
authors.lastname: Rössler
authors.forename: Heinrich
authors.initials: H
authors.lastname: Frauenknecht
authors.forename: Anja
authors.initials: A
authors.lastname: Golbeck
authors.forename: Brigitte
authors.initials: B
authors.lastname: Lechner
authors.forename: Gerhard
authors.initials: G
authors.lastname: Eigenstetter
authors.forename: Colette
authors.initials: C
authors.lastname: Zobywalski
authors.forename: Stephan
authors.initials: S
authors.lastname: Müller-Weihrich
authors.forename: Ulrike
authors.initials: U
authors.lastname: Graubner
authors.forename: Irene
authors.initials: I
authors.lastname: Schmid
authors.forename: Dieter
authors.initials: D
authors.lastname: Sackerer
authors.forename: Manfred
authors.initials: M
authors.lastname: Späth
authors.forename: Claudia
authors.initials: C
authors.lastname: Goetz
authors.forename: Franz
authors.initials: F
authors.lastname: Prantl
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Asmuss
authors.forename: Karl
authors.initials: K
authors.lastname: Bise
authors.forename: Josef
authors.initials: J
authors.lastname: Mautner
mesh_terms: 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
chemical_list: 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