Pattern of Serum Autoantibodies Allows Accurate Distinction between a Tumor and Pathologies of the Same Organ

Ludwig, Nicole; Keller, Andreas; Comtesse, Nicole; Rheinheimer, Stefanie; Pallasch, Christian P.; Fischer, Ulrike; Faßbender, Klaus; Steudel, W. I.; Lenhof, Hans‐Peter; Meese, Eckart

doi:10.1158/1078-0432.ccr-07-4715

Cited by 26 publications

(25 citation statements)

References 30 publications

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“…The hypothesis that SNPs are associated with immunogenic antigens was first proposed by Stadler et al [25]. This idea is also supported by our finding of SNPs in genes previously associated with humoral immune response in glioma patients [26], [35].…”

Section: Discussionsupporting

confidence: 84%

“…We selected a total of 132 genes including 21 genes associated with an anti-tumor humoral immune response in glioma [ 26 ] , 55 genes associated with an immune response in glioma or other brain tumors [ 35] –[37] , and 53 genes shown to be amplified or abnormally expressed in glioblastoma. (For specific details on the selection criteria of specific genes, see Table S1).…”

Section: Methodsmentioning

confidence: 99%

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Identification of Novel SNPs in Glioblastoma Using Targeted Resequencing

et al. 2011

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High-throughput sequencing opens avenues to find genetic variations that may be indicative of an increased risk for certain diseases. Linking these genomic data to other “omics” approaches bears the potential to deepen our understanding of pathogenic processes at the molecular level. To detect novel single nucleotide polymorphisms (SNPs) for glioblastoma multiforme (GBM), we used a combination of specific target selection and next generation sequencing (NGS). We generated a microarray covering the exonic regions of 132 GBM associated genes to enrich target sequences in two GBM tissues and corresponding leukocytes of the patients. Enriched target genes were sequenced with Illumina and the resulting reads were mapped to the human genome. With this approach we identified over 6000 SNPs, including over 1300 SNPs located in the targeted genes. Integrating the genome-wide association study (GWAS) catalog and known disease associated SNPs, we found that several of the detected SNPs were previously associated with smoking behavior, body mass index, breast cancer and high-grade glioma. Particularly, the breast cancer associated allele of rs660118 SNP in the gene SART1 showed a near doubled frequency in glioblastoma patients, as verified in an independent control cohort by Sanger sequencing. In addition, we identified SNPs in 20 of 21 GBM associated antigens providing further evidence that genetic variations are significantly associated with the immunogenicity of antigens.

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Section: Discussionsupporting

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Identification of Novel SNPs in Glioblastoma Using Targeted Resequencing

et al. 2011

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“…Serum-autoantibody tests hold the potential to recognize array bound peptides differentially dependent on whether these antibodies were produced in sera of control individuals or patients with a cancerous disease. These peptide sequences may serve as useful biomarkers and soon could support clinical diagnoses [38,39]. …”

Section: Discussionmentioning

confidence: 99%

Methyl-binding domain protein-based DNA isolation from human blood serum combines DNA analyses and serum-autoantibody testing

et al. 2011

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BackgroundCirculating cell free DNA in serum as well as serum-autoantibodies and the serum proteome have great potential to contribute to early cancer diagnostics via non invasive blood tests. However, most DNA preparation protocols destroy the protein fraction and therefore do not allow subsequent protein analyses. In this study a novel approach based on methyl binding domain protein (MBD) is described to overcome the technical difficulties of combining DNA and protein analysis out of one single serum sample.MethodsSerum or plasma samples from 98 control individuals and 54 breast cancer patients were evaluated upon silica membrane- or MBD affinity-based DNA isolation via qPCR targeting potential DNA methylation markers as well as by protein-microarrays for tumor-autoantibody testing.ResultsIn control individuals, an average DNA level of 22.8 ± 25.7 ng/ml was detected applying the silica membrane based protocol and 8.5 ± 7.5 ng/ml using the MBD-approach, both values strongly dependent on the serum sample preparation methods used. In contrast to malignant and benign tumor serum samples, cell free DNA concentrations were significantly elevated in sera of metastasizing breast cancer patients. Technical evaluation revealed that serum upon MBD-based DNA isolation is suitable for protein-array analyses when data are consistent to untreated serum samples.ConclusionMBD affinity purification allows DNA isolations under native conditions retaining the protein function, thus for example enabling combined analyses of DNA methylation and autoantigene-profiles from the same serum sample and thereby improving minimal invasive diagnostics.

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“…A classification of glioma sera versus sera of patients with other intracranial tumor yielded an accuracy of 88.0%. A classification between glioma sera and sera of patients with non-tumor brain pathologies yielded an accuracy of 87.8% [31]. Lung cancer and patients with non-tumor lung pathologies were separated with an accuracy of 88.5% [28].…”

Section: Introductionmentioning

confidence: 99%

Autoantibody Signature Differentiates Wilms Tumor Patients from Neuroblastoma Patients

et al. 2011

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Several studies report autoantibody signatures in cancer. The majority of these studies analyzed adult tumors and compared the seroreactivity pattern of tumor patients with the pattern in healthy controls. Here, we compared the autoimmune response in patients with neuroblastoma and patients with Wilms tumor representing two different childhood tumors. We were able to differentiate untreated neuroblastoma patients from untreated Wilms tumor patients with an accuracy of 86.8%, a sensitivity of 87.0% and a specificity of 86.7%. The separation of treated neuroblastoma patients from treated Wilms tumor patients' yielded comparable results with an accuracy of 83.8%. We furthermore identified the antigens that contribute most to the differentiation between both tumor types. The analysis of these antigens revealed that neuroblastoma was considerably more immunogenic than Wilms tumor. The reported antigens have not been found to be relevant for comparative analyses between other tumors and controls. In summary, neuroblastoma appears as a highly immunogenic tumor as demonstrated by the extended number of antigens that separate this tumor from Wilms tumor.

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Pattern of Serum Autoantibodies Allows Accurate Distinction between a Tumor and Pathologies of the Same Organ

Cited by 26 publications

References 30 publications

Identification of Novel SNPs in Glioblastoma Using Targeted Resequencing

Identification of Novel SNPs in Glioblastoma Using Targeted Resequencing

Methyl-binding domain protein-based DNA isolation from human blood serum combines DNA analyses and serum-autoantibody testing

Autoantibody Signature Differentiates Wilms Tumor Patients from Neuroblastoma Patients

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