DNA copy number profiles and systems biology connect chromatin remodeling and DNA repair in high-risk neuroblastoma

Abstract

Abstract Neuroblastoma (NB) is a solid tumor that accounts for 15% of all pediatric oncological deaths, and much is due to the low response to therapy in relapsed tumors. High-risk NB may present deletions in chromosome 11q, which may be associated with other chromosomal alterations and a poor response to therapy, but this association is still poorly understood. Using a systems biology network approach, we studied three patients with high-risk NB with deleted 11q stage 4 to highlight the connections between treatment resistance and copy number alterations in distinct cases. We built different protein-protein interaction networks for each patient based on protein-coding genes mapped at the cytobands pre- and post-chemotherapy from distinct copy number alterations data. In the post-chemotherapy networks, we identified five common regulatory nodes corresponding to the gained region located in ch17q:BIRC5, BRCA1, PRKCA, SUMO2, andGPS1. A crosslink between DNA damage and chromatin remodeling proteins was also found - a connection still poorly understood in NB. We identified a potential connection between XPB gain and chemoresistance of NB. The findings help elucidate the molecular profiles of high-risk NB with 11q deletion in pre- and post-chemotherapy tumor samples, which may reflect unique profiles in poor response to treatment.

Keywords

• Pediatric cancer
• chemotherapy
• biological networks
• drug resistance
• DNA repair.