Pediatric glioblastoma multiforme (pGBM) (AKA pediatric hemispheric high-grade glioma) is a malignant (WHO grade IV) tumor. It accounts for about 3% of primary brain tumors in children in the United States. The median survival of children with GBM ranges from 13 to 20 months, with the vast majority succumbing to the disease. Despite extensive research, we know very little about which and how human neural cells regulate pGBM cell propagation in the brain.

Although there have been significant strides made in treating pediatric cancer, a large number of children still succumb to their disease.  Moreover, survivors can have detrimental late effects from their chemotherapy and radiation including abnormal growth and development and acquisition of secondary cancers.  Therefore, improved and less toxic treatments are urgently needed.  A common event leading to pediatric cancer is the breakage of two chromosome and swapping of genetic material between ends.

Rhabdomyosarcoma (RMS) is a pediatric tumor reminiscent of immature skeletal muscle. The most aggressive subtype contains gene fusions between PAX3/7 and FOXO1 (termed fusion protein RMS or FP-RMS), which predict poor 5-year survival rates approximated at 20-30% that have not significantly improved in several decades. Therapy for the aggressive RMS subtype relies upon surgery, radiation, and toxic drugs including vincristine (targeting microtubules and inhibiting mitosis), actinomycin (non-specific inhibitor of gene expression), and cyclophosphamide (crosslinking DNA).

Desmoplastic small round cell tumor (DSRCT) is one of the most aggressive pediatric sarcomas with a low survival rates despite the combination of aggressive chemotherapy, surgery, and radiation therapy. No targeted treatments are currently available and little is known about the biology of this tumor type. Although all patients harbor a very specific chromosomal rearrangements that generates a novel fusion gene, how this gene induces the development of cancer remains a mystery.

Medulloblastoma (MB) is a devastating tumor of the cerebellum and is the most common malignant childhood brain tumor. It is a major cause of disease and mortality in children. There are currently limited options for therapy, consisting of surgical resection, radiotherapy in patients over 36 months, and chemotherapy. SHH-subtype medulloblastoma arises from a particular cell type in the cerebellum called the Granule Cell Progenitor (GCP) and accounts for 30% of all MB. It tends to arise in very young children and have a poor prognosis.