Non-myogenic tumors display altered expression of dystrophin (DMD) and a high frequency of genetic alterations

LUCE LEONELA N; GILIBERTO FLORENCIA; COTIGNOLA JAVIER; ABBATE MERCEDES

Oncotarget

Nueva York

Lugar: Nueva York; Año: 2016

ABSTRACTDMD gene mutations have been associated with the development ofDystrophinopathies. Interestingly, it has been recently reported that DMD is involvedin the development and progression of myogenic tumors, assigning DMD a tumorsuppressor activity in these types of cancer. However, there are only few reportsthat analyze DMD in non-myogenic tumors. Our study was designed to examine DMDexpression and genetic alterations in non-myogenic tumors using public repositories.We also evaluated the overall survival of patients with and without DMD mutations.We studied 59 gene expression microarrays (GEO database) and RNAseq (cBioPortal)datasets that included 9817 human samples. We found reduced DMD expression in15/27 (56%) pairwise comparisons performed (Fold-Change (FC) ≤ 0.70; p-valuerange = 0.04-1.5x10-20). The analysis of RNAseq studies revealed a median frequencyof DMD genetic alterations of 3.4%, higher or similar to other well-known tumorsuppressor genes. In addition, we observed significant poorer overall survival forpatients with DMD mutations. The analyses of paired tumor/normal tissues showedthat the majority of tumor specimens had lower DMD expression compared to theirnormal adjacent counterpart. Interestingly, statistical significant over-expression ofDMD was found in 6/27 studies (FC ≥ 1.4; p-value range = 0.03-3.4x10-15). Theseresults support that DMD expression and genetic alterations are frequent and relevantin non-myogenic tumors. The study and validation of DMD as a new player in tumordevelopment and as a new prognostic factor for tumor progression and survival arewarranted.