Medulloblastoma is a paediatric brain tumour arising in the cerebellum that predominantly occurs in males. While current protocols are very effective at treating these tumours, they result in debilitating and life-long impairment for patients. Worldwide collaborative efforts to characterise medulloblastoma tumours in greater molecular detail are leading to clinical trials with targeted therapeutics.
Sonic Hedgehog (SHh) Medulloblastoma accounts for one third of patients and is characterised by excessive signalling through the SHh pathway. This is recapitulated in mice that are heterozygous for Ptch1. When we removed STAT3 from the originating cell of this disease, cerebellar granule precursors, using a cell-type specific Cre-Lox system tumour survival increased in males but not female mice, suggesting a sex-specific role for STAT3 in SHh medulloblastoma. Importantly when SHh Medulloblastoma patient samples were stratified on the basis of sex and STAT3 expression we observe that males with low STAT3 have significantly longer overall survival, whereas outcomes for female patients are not significantly altered on the basis of STAT3 expression.
Using transcriptomic data sets from a SHh medulloblastoma cohort we have identified STAT3-dependent genes that are specific to males and correlate with overall survival. Analysis of whether altering expression of these transcripts affects tumour development are presently under way. This is the first observation of a gene that could, in part, explain the sex dimorphism in this disease and offer insights into altered treatment options for patients on the basis of their sex and/or STAT3 expression.