The protein phosphatase 2A regulatory subunit PR70 is a gonosomal melanoma tumor suppressor gene

Men with melanoma have a significantly worse prognosis than women, and the biological underpinnings of this difference are unknown. The current study demonstrates that loss of the inactivated X chromosome in melanomas arising in females is strongly associated with poor distant metastasis free survival. High expression of the gonosomal PPP2R3B gene, a gene that escapes inactivation, is independently correlated with survival. PPP2R3B downregulates melanoma growth by negatively interfering with DNA replication and cell cycle progression through its role in stabilizing CDC6/CDT1 interaction during the replication origins firing and as such behaves functionally as a tumor suppressor gene. Fourty-nine fresh frozen primary melanoma samples were profiled by CGH array using sex-matched commercial DNA as reference.