Heterogeneity and tumoral origin of medulloblastoma in the single-cell era

Abstract

Medulloblastoma is one of the most common malignant pediatric brain tumors derived from posterior fossa. The current treatment includes maximal safe surgical resection, radiotherapy, whole cranio-spinal radiation and adjuvant with chemotherapy. However, it can only limitedly prolong the survival time with severe side effects and relapse. Defining the intratumoral heterogeneity, cellular origin and identifying the interaction network within tumor microenvironment are helpful for understanding the mechanisms of medulloblastoma tumorigenesis and relapse. Due to technological limitations, the mechanisms of cellular heterogeneity and tumor origin have not been fully understood. Recently, the emergence of single-cell technology has provided a powerful tool for achieving the goal of understanding the mechanisms of tumorigenesis. Several studies have demonstrated the intratumoral heterogeneity and tumor origin for each subtype of medulloblastoma utilizing the single-cell RNA-seq, which has not been uncovered before using conventional technologies. In this review, we present an overview of the current progress in understanding of cellular heterogeneity and tumor origin of medulloblastoma and discuss novel findings in the age of single-cell technologies.

Overcoming Treatment Resistance in Medulloblastoma: Underlying Mechanisms and Potential Strategies

“…The clonal heterogeneity of tumors has long been studied as one of the major contributors to treatment resistance in cancer and one of the main reasons behind the failure of certain targeted therapies despite preclinical promise. The revolution in ability to profile the molecular, genetic, and epigenetic landscape at the single cell level brought the importance of intra and intertumoral heterogeneity into the light, and since then, great leaps have been made to discover this heterogeneity at various levels [ 76 ]. In this context, Hovestadt et al characterized the different metaprograms that dominate the transcriptional landscape of each subtype of medulloblastoma ( Figure 2 ).…”