Abstract
AbstractMedulloblastoma is the most common childhood malignant brain tumour, and represents 20% of all paediatric central nervous system neoplasms. Although advances in surgery, radiation and chemotherapy have improved overall survival, the lifelong sequelae of these treatments represents a major health care burden for patients, parents, and society. Recent progress in the molecular subtyping of medulloblastoma have revealed at least four distinct subsets of tumours with dramatically different biology. Additionally, medulloblastoma predominately occurs in males and maleness correlates with worse outcome. However, the drivers of this sexual dimorphism in medulloblastoma are unclear. We have identified that STAT3 is one such factor. Deletion of STAT3 from granule cell precursors in a mouse model of SHh medulloblastoma driven by the loss of one PTCH1 allele results in complete protection of males, but has no effect in females. Stratification of transcriptomics data from a cohort of SHh medulloblastoma patients on the basis of STAT3 expression shows that male patients with low STAT3 expression have improved overall survival - an outcome not observed in females. Additionally, we identified STAT3-dependent genes, specific to males which correlate with overall survival. This is one of the first observations of a gene that could, in part, explain the sex dimorphism in medulloblastoma and offer insights into altered treatment options for patients on the basis of their sex and/or STAT3 expression.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
