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Genomic Heterogeneity of Osteosarcoma - Shift from Single Candidates to Functional Modules
Osteosarcoma (OS), a bone tumor, exhibit a complex karyotype. On the genomic level a highly variable degree of alterations in nearly all chromosomal regions and between individual tumors is observable. This hampers the identification of common drivers in OS biology. To identify the common molecular...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388529/ https://www.ncbi.nlm.nih.gov/pubmed/25848766 http://dx.doi.org/10.1371/journal.pone.0123082 |
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author | Poos, Kathrin Smida, Jan Maugg, Doris Eckstein, Gertrud Baumhoer, Daniel Nathrath, Michaela Korsching, Eberhard |
author_facet | Poos, Kathrin Smida, Jan Maugg, Doris Eckstein, Gertrud Baumhoer, Daniel Nathrath, Michaela Korsching, Eberhard |
author_sort | Poos, Kathrin |
collection | PubMed |
description | Osteosarcoma (OS), a bone tumor, exhibit a complex karyotype. On the genomic level a highly variable degree of alterations in nearly all chromosomal regions and between individual tumors is observable. This hampers the identification of common drivers in OS biology. To identify the common molecular mechanisms involved in the maintenance of OS, we follow the hypothesis that all the copy number-associated differences between the patients are intercepted on the level of the functional modules. The implementation is based on a network approach utilizing copy number associated genes in OS, paired expression data and protein interaction data. The resulting functional modules of tightly connected genes were interpreted regarding their biological functions in OS and their potential prognostic significance. We identified an osteosarcoma network assembling well-known and lesser-known candidates. The derived network shows a significant connectivity and modularity suggesting that the genes affected by the heterogeneous genetic alterations share the same biological context. The network modules participate in several critical aspects of cancer biology like DNA damage response, cell growth, and cell motility which is in line with the hypothesis of specifically deregulated but functional modules in cancer. Further, we could deduce genes with possible prognostic significance in OS for further investigation (e.g. EZR, CDKN2A, MAP3K5). Several of those module genes were located on chromosome 6q. The given systems biological approach provides evidence that heterogeneity on the genomic and expression level is ordered by the biological system on the level of the functional modules. Different genomic aberrations are pointing to the same cellular network vicinity to form vital, but already neoplastically altered, functional modules maintaining OS. This observation, exemplarily now shown for OS, has been under discussion already for a longer time, but often in a hypothetical manner, and can here be exemplified for OS. |
format | Online Article Text |
id | pubmed-4388529 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43885292015-04-21 Genomic Heterogeneity of Osteosarcoma - Shift from Single Candidates to Functional Modules Poos, Kathrin Smida, Jan Maugg, Doris Eckstein, Gertrud Baumhoer, Daniel Nathrath, Michaela Korsching, Eberhard PLoS One Research Article Osteosarcoma (OS), a bone tumor, exhibit a complex karyotype. On the genomic level a highly variable degree of alterations in nearly all chromosomal regions and between individual tumors is observable. This hampers the identification of common drivers in OS biology. To identify the common molecular mechanisms involved in the maintenance of OS, we follow the hypothesis that all the copy number-associated differences between the patients are intercepted on the level of the functional modules. The implementation is based on a network approach utilizing copy number associated genes in OS, paired expression data and protein interaction data. The resulting functional modules of tightly connected genes were interpreted regarding their biological functions in OS and their potential prognostic significance. We identified an osteosarcoma network assembling well-known and lesser-known candidates. The derived network shows a significant connectivity and modularity suggesting that the genes affected by the heterogeneous genetic alterations share the same biological context. The network modules participate in several critical aspects of cancer biology like DNA damage response, cell growth, and cell motility which is in line with the hypothesis of specifically deregulated but functional modules in cancer. Further, we could deduce genes with possible prognostic significance in OS for further investigation (e.g. EZR, CDKN2A, MAP3K5). Several of those module genes were located on chromosome 6q. The given systems biological approach provides evidence that heterogeneity on the genomic and expression level is ordered by the biological system on the level of the functional modules. Different genomic aberrations are pointing to the same cellular network vicinity to form vital, but already neoplastically altered, functional modules maintaining OS. This observation, exemplarily now shown for OS, has been under discussion already for a longer time, but often in a hypothetical manner, and can here be exemplified for OS. Public Library of Science 2015-04-07 /pmc/articles/PMC4388529/ /pubmed/25848766 http://dx.doi.org/10.1371/journal.pone.0123082 Text en © 2015 Poos et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Poos, Kathrin Smida, Jan Maugg, Doris Eckstein, Gertrud Baumhoer, Daniel Nathrath, Michaela Korsching, Eberhard Genomic Heterogeneity of Osteosarcoma - Shift from Single Candidates to Functional Modules |
title | Genomic Heterogeneity of Osteosarcoma - Shift from Single Candidates to Functional Modules |
title_full | Genomic Heterogeneity of Osteosarcoma - Shift from Single Candidates to Functional Modules |
title_fullStr | Genomic Heterogeneity of Osteosarcoma - Shift from Single Candidates to Functional Modules |
title_full_unstemmed | Genomic Heterogeneity of Osteosarcoma - Shift from Single Candidates to Functional Modules |
title_short | Genomic Heterogeneity of Osteosarcoma - Shift from Single Candidates to Functional Modules |
title_sort | genomic heterogeneity of osteosarcoma - shift from single candidates to functional modules |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388529/ https://www.ncbi.nlm.nih.gov/pubmed/25848766 http://dx.doi.org/10.1371/journal.pone.0123082 |
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