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

DMD gene mutations have been associated with the development of Dystrophinopathies. Interestingly, it has been recently reported that DMD is involved in the development and progression of myogenic tumors, assigning DMD a tumor suppressor activity in these types of cancer. However, there are only few...

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Autores principales: Luce, Leonela N., Abbate, Mercedes, Cotignola, Javier, Giliberto, Florencia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352069/
https://www.ncbi.nlm.nih.gov/pubmed/27391342
http://dx.doi.org/10.18632/oncotarget.10426
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author Luce, Leonela N.
Abbate, Mercedes
Cotignola, Javier
Giliberto, Florencia
author_facet Luce, Leonela N.
Abbate, Mercedes
Cotignola, Javier
Giliberto, Florencia
author_sort Luce, Leonela N.
collection PubMed
description DMD gene mutations have been associated with the development of Dystrophinopathies. Interestingly, it has been recently reported that DMD is involved in the development and progression of myogenic tumors, assigning DMD a tumor suppressor activity in these types of cancer. However, there are only few reports that analyze DMD in non-myogenic tumors. Our study was designed to examine DMD expression 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 in 15/27 (56%) pairwise comparisons performed (Fold-Change (FC) ≤ 0.70; p-value range = 0.04-1.5×10(−20)). The analysis of RNAseq studies revealed a median frequency of DMD genetic alterations of 3.4%, higher or similar to other well-known tumor suppressor genes. In addition, we observed significant poorer overall survival for patients with DMD mutations. The analyses of paired tumor/normal tissues showed that the majority of tumor specimens had lower DMD expression compared to their normal adjacent counterpart. Interestingly, statistical significant over-expression of DMD was found in 6/27 studies (FC ≥ 1.4; p-value range = 0.03-3.4×10(−15)). These results support that DMD expression and genetic alterations are frequent and relevant in non-myogenic tumors. The study and validation of DMD as a new player in tumor development and as a new prognostic factor for tumor progression and survival are warranted.
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spelling pubmed-53520692017-04-13 Non-myogenic tumors display altered expression of dystrophin (DMD) and a high frequency of genetic alterations Luce, Leonela N. Abbate, Mercedes Cotignola, Javier Giliberto, Florencia Oncotarget Research Paper DMD gene mutations have been associated with the development of Dystrophinopathies. Interestingly, it has been recently reported that DMD is involved in the development and progression of myogenic tumors, assigning DMD a tumor suppressor activity in these types of cancer. However, there are only few reports that analyze DMD in non-myogenic tumors. Our study was designed to examine DMD expression 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 in 15/27 (56%) pairwise comparisons performed (Fold-Change (FC) ≤ 0.70; p-value range = 0.04-1.5×10(−20)). The analysis of RNAseq studies revealed a median frequency of DMD genetic alterations of 3.4%, higher or similar to other well-known tumor suppressor genes. In addition, we observed significant poorer overall survival for patients with DMD mutations. The analyses of paired tumor/normal tissues showed that the majority of tumor specimens had lower DMD expression compared to their normal adjacent counterpart. Interestingly, statistical significant over-expression of DMD was found in 6/27 studies (FC ≥ 1.4; p-value range = 0.03-3.4×10(−15)). These results support that DMD expression and genetic alterations are frequent and relevant in non-myogenic tumors. The study and validation of DMD as a new player in tumor development and as a new prognostic factor for tumor progression and survival are warranted. Impact Journals LLC 2016-07-06 /pmc/articles/PMC5352069/ /pubmed/27391342 http://dx.doi.org/10.18632/oncotarget.10426 Text en Copyright: © 2017 Luce et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Luce, Leonela N.
Abbate, Mercedes
Cotignola, Javier
Giliberto, Florencia
Non-myogenic tumors display altered expression of dystrophin (DMD) and a high frequency of genetic alterations
title Non-myogenic tumors display altered expression of dystrophin (DMD) and a high frequency of genetic alterations
title_full Non-myogenic tumors display altered expression of dystrophin (DMD) and a high frequency of genetic alterations
title_fullStr Non-myogenic tumors display altered expression of dystrophin (DMD) and a high frequency of genetic alterations
title_full_unstemmed Non-myogenic tumors display altered expression of dystrophin (DMD) and a high frequency of genetic alterations
title_short Non-myogenic tumors display altered expression of dystrophin (DMD) and a high frequency of genetic alterations
title_sort non-myogenic tumors display altered expression of dystrophin (dmd) and a high frequency of genetic alterations
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352069/
https://www.ncbi.nlm.nih.gov/pubmed/27391342
http://dx.doi.org/10.18632/oncotarget.10426
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