Clinical Trials
Antigen scenario of the SIOP clinical trial (Norbert Graf – USAAR)
Wilms tumour is the most common malignant renal tumour in children. In the SIOP 2001/ GPOH trial clinical data, molecular data and pre- and post-chemotherapy DICOM imaging studies are collected, coming from patients out of more than 50 hospitals in Germany. Since 2009 anonymized data of the SIOP/GPOH trial are used in the ACGT scenarios. From a limited set of these patients, microarray data and data of autoantibodies against tumour specific antigens of Wilms tumour are provided. The main question is to answer whether molecular biology helps to define new risk groups in Wilms tumour and can be used to stratify treatment of these patients in the future. As ACGT promotes the integration of heterogeneous data and provides necessary analytic tools, it facilitates further molecular analysis and allows clinicians to efficiently analyze data that are presently communicated by mail, fax or maintained in flat text files at various remote clinical sites.
One of the scenarios that are analyzed in ACGT is the Antigen scenario, to analyze if autoantibodies against tumour specific antigens do correlate with histology and outcome. Up to now in 133 patients we did receive serum for the Antigen scenario. Altogether 355 sera are collected from 265 patients out of 36 local hospitals. Out of this cohort 72 sera were from healthy children and 60 from patients suffering from other cancers than nephroblastoma. These sera are used as a control groups. Most of the sera are collected at the time of diagnosis. A preliminary analysis of the Antigen Scenario regarding the characterization of found autoantigens against nephroblastoma was reported at the Nephroblastoma meeting in Chamonix, France in March 2008 and at the SIOP conference in Berlin in October 2008. In contrast to adult patients one can find more autoantigens in sera of children. This is shown in figure 1. The same autoantigen can be found in a higher frequency in children and children with cancer than in adult cancer patients. 61 clones could be found that discriminates between nephroblastoma and neuroblastoma. 39 of these clones can be selected as best discrimators. Figure 2 shows for a single antigen the discrimination between sera of patients with nephroblastoma and neuroblastoma.
Figure 1: Frequency of autoantibodies found in sera of patients.
Figure 2: Discrimination between nephroblastoma and neuroblastoma shown for 1 antigen in different sera of patients.
Between healthy children and patients with nephro- or neuroblastoma there is an overlapping of autoantibodies. But one can find single autoantibodies that are only expressed in single diseases as shown in figure 3.
Figure 3: Overlapping of antigens between healthy children and patients with nephro- and neuroblastoma.
Taking these results together, we hope that we will find a pattern of autoantibodies that is predictive for a correct diagnosis of Wilms tumour and correlates to the outcome of patients. Together with microarray data a scenario is currently under development in ACGT to analyze these heterogeneous and distributed data together with the corresponding clinical data and data from the KEGG database to find new insights in the biology of Wilms tumour. Results of this scenario will be presented at the next Wilms Tumour Biology Meeting taking place in March 2010 in Banff/Canada.