National Lottery helps funding prognostic neuroblastoma test
Neuroblastoma is a rare childhood tumor of the peripheral nervous system and accounts for approximately 15% of all childhood cancer related deaths. Although international collaboration in the field of neuroblastoma has put a tremendous effort in optimizing patient stratification and therapy protocols, overall survival rates remain low. In this context, the Center for Medical Genetics Ghent aims to identify and validate additional markers for risk stratification, as this will allow clinicians to better select accurate therapies, leading to increased effectiveness of cancer treatment strategies.
Firstly, small circulating nucleic acid fragments in serum called microRNAs (miRNAs) are evaluated. This is done by determining quantitative differences between patients with fatal outcome and patients in complete remission, to select for miRNAs with the largest difference between the groups. These miRNA are then tested in independent patient groups for their ability to predict patient outcome for construction of a prognostic biomarker. To this purpose, the team tested 87 serum samples for 1805 miRNA and was able to select 377 miRNAs as promising candidate biomarkers. These biomarkers are currently being evaluated in independent patient groups for establishment of a clinically useful classifier.
The second biological information used is “DNA methylation”. As cancer processes are characterized by specific changes in the normal DNA methylation patterns, these changes can be used as biomarkers. The team scanned the methylome of more than 100 primary neuroblastoma tumors, using a genome-wide sequencing technology, in order to identify changes specific for neuroblastoma patients with an unfavorable prognosis. These candidate prognostic DNA methylation markers were then selected for further analysis and were tested in an independent cohort of 165 primary tumors using a more specific and sensitive methylation detection methodology. Verification is ongoing, but already shows promising results.