Highlights d DRAK2 is markedly upregulated in the livers of both patients and mice with NAFLD/NASH d DRAK2 regulates RNA alternative splicing through SRPK1mediated SRSF6 phosphorylation d DRAK2 disturbs mitochondrial function in hepatic steatosis via RNA splicing machinery

BackgroundGender-based differences in disease onset in murine models of malignant peripheral nerve sheath tumor (MPNST) and in patients with Neurofibromatosis type-1-(NF-1)-associated or spontaneous MPNST has not been well studied.MethodsForty-three mGFAP-Cre+;Ptenloxp/+;LSL-K-rasG12D/+ mice were observed for tumor development and evaluated for gender disparity in age of MPNST onset. Patient data from the prospectively collected UCLA sarcoma database (1974–2011, n = 113 MPNST patients) and 39 published studies on MPNST patients (n = 916) were analyzed for age of onset differences between sexes and between NF-1 and spontaneous MPNST patients.ResultsOur murine model showed gender-based differences in MPNST onset, with males developing MPNST significantly earlier than females (142 vs. 162 days, p = 0.015). In the UCLA patient population, males also developed MPNST earlier than females (median age 35 vs. 39.5 years, p = 0.048). Patients with NF-1-associated MPNST had significantly earlier age of onset compared to spontaneous MPNST (median age 33 vs. 39 years, p = 0.007). However, expanded analysis of 916 published MPNST cases revealed no significant age difference in MPNST onset between males and females. Similar to the UCLA dataset, patients with NF-1 developed MPNST at a significantly younger age than spontaneous MPNST patients (p < 0.0001, median age 28 vs. 41 years) and this disparity was maintained across North American, European, and Asian populations.ConclusionsAlthough our preclinical model and single-institution patient cohort show gender dimorphism in MPNST onset, no significant gender disparity was detected in the larger MPNST patient meta-dataset. NF-1 patients develop MPNST 13 years earlier than patients with spontaneous MPNST, with little geographical variance.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-827) contains supplementary material, which is available to authorized users.