Intratumoral heterogeneity in recurrent pediatric pilocytic astrocytomas

Cancer tumors are composed by a wide variety of cells with genetic and transcriptional alterations accumulated throughout tumor progression. This intra-tumoral heterogeneity provides adaptability of the tumor. Cell niches enriched with transcriptional signatures for cell renewal, adaptation and resistance to DNA damage induced by radiation (radiotherapy resistance) have been identified within some cancer tumors. Therefore, it seems that intra-tumoral heterogeneity imposes deep challenges to current therapeutic treatments. Tumors of the central nervous system are the most common solid tumors during childhood and are in the top-two causes of cancer-related death in children worldwide. Gliomas arise from glial precursor cells that are present in the brain and spinal cord and astrocytoma is the most commonly diagnosed type of glioma in children. Despite similar origin, astrocytomas behave differently depending on their location. Pilocytic astrocytoma that arise in cerebellum are more resilient and display a higher relapse degree after removal compared to those ones that arise in cerebrum. We will compare the transcritome of single nuclei from pediatric pilocytic astrocytoma from cerebellum in two time points (i.e., newly diagnosed vs relapse) plus healthy tissues. We predict that cells that produce tumor relapse will be present in both time points. Therefore, based on their transcriptional profiles, we will be able to identify them. This information will provide a deep knowledge about tumor relapse that can be extrapolated to other tumors and will offer RNA biomarkers for therapeutic purposes.

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