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Sodium ion channel mutations in glioblastoma patients correlate with shorter survival
BACKGROUND: Glioblastoma Multiforme (GBM) is the most common and invasive astrocytic tumor associated with dismal prognosis. Treatment for GBM patients has advanced, but the median survival remains a meager 15 months. In a recent study, 20,000 genes from 21 GBM patients were sequenced that identifie...
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050859/ https://www.ncbi.nlm.nih.gov/pubmed/21314958 http://dx.doi.org/10.1186/1476-4598-10-17 |
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author | Joshi, Avadhut D Parsons, D Williams Velculescu, Victor E Riggins, Gregory J |
author_facet | Joshi, Avadhut D Parsons, D Williams Velculescu, Victor E Riggins, Gregory J |
author_sort | Joshi, Avadhut D |
collection | PubMed |
description | BACKGROUND: Glioblastoma Multiforme (GBM) is the most common and invasive astrocytic tumor associated with dismal prognosis. Treatment for GBM patients has advanced, but the median survival remains a meager 15 months. In a recent study, 20,000 genes from 21 GBM patients were sequenced that identified frequent mutations in ion channel genes. The goal of this study was to determine whether ion channel mutations have a role in disease progression and whether molecular targeting of ion channels is a promising therapeutic strategy for GBM patients. Therefore, we compared GBM patient survival on the basis of presence or absence of mutations in calcium, potassium and sodium ion transport genes. Cardiac glycosides, known sodium channel inhibitors, were then tested for their ability to inhibit GBM cell proliferation. RESULTS: Nearly 90% of patients showed at least one mutation in ion transport genes. GBM patients with mutations in sodium channels showed a significantly shorter survival compared to patients with no sodium channel mutations, whereas a similar comparison based on mutational status of calcium or potassium ion channel mutations showed no survival differences. Experimentally, targeting GBM cells with cardiac glycosides such as digoxin and ouabain demonstrated preferential cytotoxicity against U-87 and D54 GBM cells compared to non-tumor astrocytes (NTAs). CONCLUSIONS: These pilot studies of GBM patients with sodium channel mutations indicate an association with a more aggressive disease and significantly shorter survival. Moreover, inhibition of GBM cells by ion channel inhibitors such as cardiac glycosides suggest a therapeutic strategy with relatively safe drugs for targeting GBM ion channel mutations. Key Words: glioblastoma multiforme, ion channels, mutations, small molecule inhibitors, cardiac glycosides. |
format | Text |
id | pubmed-3050859 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-30508592011-03-09 Sodium ion channel mutations in glioblastoma patients correlate with shorter survival Joshi, Avadhut D Parsons, D Williams Velculescu, Victor E Riggins, Gregory J Mol Cancer Research BACKGROUND: Glioblastoma Multiforme (GBM) is the most common and invasive astrocytic tumor associated with dismal prognosis. Treatment for GBM patients has advanced, but the median survival remains a meager 15 months. In a recent study, 20,000 genes from 21 GBM patients were sequenced that identified frequent mutations in ion channel genes. The goal of this study was to determine whether ion channel mutations have a role in disease progression and whether molecular targeting of ion channels is a promising therapeutic strategy for GBM patients. Therefore, we compared GBM patient survival on the basis of presence or absence of mutations in calcium, potassium and sodium ion transport genes. Cardiac glycosides, known sodium channel inhibitors, were then tested for their ability to inhibit GBM cell proliferation. RESULTS: Nearly 90% of patients showed at least one mutation in ion transport genes. GBM patients with mutations in sodium channels showed a significantly shorter survival compared to patients with no sodium channel mutations, whereas a similar comparison based on mutational status of calcium or potassium ion channel mutations showed no survival differences. Experimentally, targeting GBM cells with cardiac glycosides such as digoxin and ouabain demonstrated preferential cytotoxicity against U-87 and D54 GBM cells compared to non-tumor astrocytes (NTAs). CONCLUSIONS: These pilot studies of GBM patients with sodium channel mutations indicate an association with a more aggressive disease and significantly shorter survival. Moreover, inhibition of GBM cells by ion channel inhibitors such as cardiac glycosides suggest a therapeutic strategy with relatively safe drugs for targeting GBM ion channel mutations. Key Words: glioblastoma multiforme, ion channels, mutations, small molecule inhibitors, cardiac glycosides. BioMed Central 2011-02-11 /pmc/articles/PMC3050859/ /pubmed/21314958 http://dx.doi.org/10.1186/1476-4598-10-17 Text en Copyright ©2011 Joshi et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Joshi, Avadhut D Parsons, D Williams Velculescu, Victor E Riggins, Gregory J Sodium ion channel mutations in glioblastoma patients correlate with shorter survival |
title | Sodium ion channel mutations in glioblastoma patients correlate with shorter survival |
title_full | Sodium ion channel mutations in glioblastoma patients correlate with shorter survival |
title_fullStr | Sodium ion channel mutations in glioblastoma patients correlate with shorter survival |
title_full_unstemmed | Sodium ion channel mutations in glioblastoma patients correlate with shorter survival |
title_short | Sodium ion channel mutations in glioblastoma patients correlate with shorter survival |
title_sort | sodium ion channel mutations in glioblastoma patients correlate with shorter survival |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050859/ https://www.ncbi.nlm.nih.gov/pubmed/21314958 http://dx.doi.org/10.1186/1476-4598-10-17 |
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