Delineating the cytogenomic and epigenomic landscapes of glioma stem cell lines.
Glioblastoma multiforme (GBM), the most common and malignant type of glioma, is characterized by a poor prognosis and the lack of an effective treatment, which are due to a small sub-population of cells with stem-like properties, termed glioma stem cells (GSCs). The term "multiforme" descr...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3585345?pdf=render |
| _version_ | 1828401765598363648 |
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| author | Simona Baronchelli Angela Bentivegna Serena Redaelli Gabriele Riva Valentina Butta Laura Paoletta Giuseppe Isimbaldi Monica Miozzo Silvia Tabano Antonio Daga Daniela Marubbi Monica Cattaneo Ida Biunno Leda Dalprà |
| author_facet | Simona Baronchelli Angela Bentivegna Serena Redaelli Gabriele Riva Valentina Butta Laura Paoletta Giuseppe Isimbaldi Monica Miozzo Silvia Tabano Antonio Daga Daniela Marubbi Monica Cattaneo Ida Biunno Leda Dalprà |
| author_sort | Simona Baronchelli |
| collection | DOAJ |
| description | Glioblastoma multiforme (GBM), the most common and malignant type of glioma, is characterized by a poor prognosis and the lack of an effective treatment, which are due to a small sub-population of cells with stem-like properties, termed glioma stem cells (GSCs). The term "multiforme" describes the histological features of this tumor, that is, the cellular and morphological heterogeneity. At the molecular level multiple layers of alterations may reflect this heterogeneity providing together the driving force for tumor initiation and development. In order to decipher the common "signature" of the ancestral GSC population, we examined six already characterized GSC lines evaluating their cytogenomic and epigenomic profiles through a multilevel approach (conventional cytogenetic, FISH, aCGH, MeDIP-Chip and functional bioinformatic analysis). We found several canonical cytogenetic alterations associated with GBM and a common minimal deleted region (MDR) at 1p36.31, including CAMTA1 gene, a putative tumor suppressor gene, specific for the GSC population. Therefore, on one hand our data confirm a role of driver mutations for copy number alterations (CNAs) included in the GBM genomic-signature (gain of chromosome 7- EGFR gene, loss of chromosome 13- RB1 gene, loss of chromosome 10-PTEN gene); on the other, it is not obvious that the new identified CNAs are passenger mutations, as they may be necessary for tumor progression specific for the individual patient. Through our approach, we were able to demonstrate that not only individual genes into a pathway can be perturbed through multiple mechanisms and at different levels, but also that different combinations of perturbed genes can incapacitate functional modules within a cellular networks. Therefore, beyond the differences that can create apparent heterogeneity of alterations among GSC lines, there's a sort of selective force acting on them in order to converge towards the impairment of cell development and differentiation processes. This new overview could have a huge importance in therapy. |
| first_indexed | 2024-12-10T09:51:25Z |
| format | Article |
| id | doaj.art-2a574df177324bcab0ceb70c67268253 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T09:51:25Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2a574df177324bcab0ceb70c672682532022-12-22T01:53:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5746210.1371/journal.pone.0057462Delineating the cytogenomic and epigenomic landscapes of glioma stem cell lines.Simona BaronchelliAngela BentivegnaSerena RedaelliGabriele RivaValentina ButtaLaura PaolettaGiuseppe IsimbaldiMonica MiozzoSilvia TabanoAntonio DagaDaniela MarubbiMonica CattaneoIda BiunnoLeda DalpràGlioblastoma multiforme (GBM), the most common and malignant type of glioma, is characterized by a poor prognosis and the lack of an effective treatment, which are due to a small sub-population of cells with stem-like properties, termed glioma stem cells (GSCs). The term "multiforme" describes the histological features of this tumor, that is, the cellular and morphological heterogeneity. At the molecular level multiple layers of alterations may reflect this heterogeneity providing together the driving force for tumor initiation and development. In order to decipher the common "signature" of the ancestral GSC population, we examined six already characterized GSC lines evaluating their cytogenomic and epigenomic profiles through a multilevel approach (conventional cytogenetic, FISH, aCGH, MeDIP-Chip and functional bioinformatic analysis). We found several canonical cytogenetic alterations associated with GBM and a common minimal deleted region (MDR) at 1p36.31, including CAMTA1 gene, a putative tumor suppressor gene, specific for the GSC population. Therefore, on one hand our data confirm a role of driver mutations for copy number alterations (CNAs) included in the GBM genomic-signature (gain of chromosome 7- EGFR gene, loss of chromosome 13- RB1 gene, loss of chromosome 10-PTEN gene); on the other, it is not obvious that the new identified CNAs are passenger mutations, as they may be necessary for tumor progression specific for the individual patient. Through our approach, we were able to demonstrate that not only individual genes into a pathway can be perturbed through multiple mechanisms and at different levels, but also that different combinations of perturbed genes can incapacitate functional modules within a cellular networks. Therefore, beyond the differences that can create apparent heterogeneity of alterations among GSC lines, there's a sort of selective force acting on them in order to converge towards the impairment of cell development and differentiation processes. This new overview could have a huge importance in therapy.http://europepmc.org/articles/PMC3585345?pdf=render |
| spellingShingle | Simona Baronchelli Angela Bentivegna Serena Redaelli Gabriele Riva Valentina Butta Laura Paoletta Giuseppe Isimbaldi Monica Miozzo Silvia Tabano Antonio Daga Daniela Marubbi Monica Cattaneo Ida Biunno Leda Dalprà Delineating the cytogenomic and epigenomic landscapes of glioma stem cell lines. PLoS ONE |
| title | Delineating the cytogenomic and epigenomic landscapes of glioma stem cell lines. |
| title_full | Delineating the cytogenomic and epigenomic landscapes of glioma stem cell lines. |
| title_fullStr | Delineating the cytogenomic and epigenomic landscapes of glioma stem cell lines. |
| title_full_unstemmed | Delineating the cytogenomic and epigenomic landscapes of glioma stem cell lines. |
| title_short | Delineating the cytogenomic and epigenomic landscapes of glioma stem cell lines. |
| title_sort | delineating the cytogenomic and epigenomic landscapes of glioma stem cell lines |
| url | http://europepmc.org/articles/PMC3585345?pdf=render |
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