'Insights into the mechanisms of tumor progression and regression using neuroblastoma as a model' - Invited speaker seminar

“Meet the PhD Jury” invited speaker seminar by prof. dr. Matthias Fischer from the Center for Molecular Medicine Cologne, University of Cologne, Germany. 

Abstract: 
Neuroblastoma is a pediatric tumor of the sympathetic nervous system. Its clinical course ranges from spontaneous tumor regression to fatal progression. To investigate the molecular features of the divergent tumor subtypes, we performed genome sequencing on 416 pretreatment neuroblastomas and integrated sequencing results with information on telomere maintenance mechanisms in 208 of these tumors. We found that patients whose tumors lacked telomere maintenance mechanisms had an excellent prognosis, whereas the prognosis of patients whose tumors harbored telomere maintenance mechanisms was substantially worse. Survival rates were lowest for neuroblastoma patients whose tumors harbored telomere maintenance mechanisms in combination with RAS and/or p53 pathway mutations. By contrast, spontaneous tumor regression occurred both in the presence and absence of RAS/p53 pathway mutations in patients with telomere maintenance-negative tumors. Based on these data, we propose a mechanistic classi fication of neuroblastoma that may benefit the clinical management of patients. In addition, our results emphasize the central role of telomere maintenance mechanisms in the pathogenesis of human malignancies.