Characterization of tumor development in MYC-driven pediatric cancer

Sammanfattning

Medulloblastomas are the most common malignant central nervous system tumors in children. The tumors are resected in neurosurgery, followed by radiation treatment and chemotherapy. Very young children and infants are omitted from this treatment due to the damaging side-effects. In order to further refine the treatment regime, medulloblastoma can be subdivided and more clearly understood as subgroups. These consist of WNT, SHH, Group 3 and Group 4. Out of these, the group 3 medulloblastomas are particularly devastating with less than 50% of patients surviving past 5 years. Gene expression studies of group 3 medulloblastoma found an overexpression of MYC, a gene regulator involved in many human cancers. The Swartling lab designed and produced the GTML and GMYC mouse models, which uses Mycn or Myc overexpression to yield fast-growing aggressive tumors in mice. Tumor penetrance was not 100% however, there was some genetic event believed to be missing from the model. The aim of this project was to characterize how these medulloblastoma models behave using image quantification of different markers in mouse brains on one hand, and to use whole exome sequencing-data to further elucidate possible mutations in the tumors which could potentially be added on to the existing mouse model. The sequencing validation results suggested mutations in an epigenetic regulator complex could be of possible interest to continue with functional studies on. The image quantification project provided a useful tool to build upon and could result in an atlas of the medulloblastoma models, complete with a plethora of different markers and timepoints.