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Genetic alterations in glioma.

Bralten LB, French PJ - Cancers (Basel) (2011)

Bottom Line: Recently, two major studies have performed in-depth mutation analysis of glioblastomas (the most common and aggressive subtype of glioma).This systematic approach revealed three major pathways that are affected in glioblastomas: The receptor tyrosine kinase signaling pathway, the TP53 pathway and the pRB pathway.Exceptions include TP53 mutations and fusion genes involving the BRAF gene in astrocytic and pilocytic glioma subtypes, respectively.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Erasmus University Medical Center, Erasmus University Rotterdam, Dr Molewaterplein 50, 3000 CA, Rotterdam, the Netherlands. p.french@erasmusmc.nl.

ABSTRACT
Gliomas are the most common type of primary brain tumor and have a dismal prognosis. Understanding the genetic alterations that drive glioma formation and progression may help improve patient prognosis by identification of novel treatment targets. Recently, two major studies have performed in-depth mutation analysis of glioblastomas (the most common and aggressive subtype of glioma). This systematic approach revealed three major pathways that are affected in glioblastomas: The receptor tyrosine kinase signaling pathway, the TP53 pathway and the pRB pathway. Apart from frequent mutations in the IDH1/2 gene, much less is known about the causal genetic changes of grade II and III (anaplastic) gliomas. Exceptions include TP53 mutations and fusion genes involving the BRAF gene in astrocytic and pilocytic glioma subtypes, respectively. In this review, we provide an update on all common events involved in the initiation and/or progression across the different subtypes of glioma and provide future directions for research into the genetic changes.

No MeSH data available.


Related in: MedlinePlus

The three major pathways affected in a high percentage of glioblastomas and the most common genes affected in those pathways. Following the gene names, the percentages of genetic alterations found in glioblastoma are depicted.
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f1-cancers-03-01129: The three major pathways affected in a high percentage of glioblastomas and the most common genes affected in those pathways. Following the gene names, the percentages of genetic alterations found in glioblastoma are depicted.

Mentions: The Cancer Genome Atlas project has published mRNA expression data and DNA copy number alteration data of 206 GBMs and has sequenced >600 genes in 91 GBMs [6]. The project is still ongoing and ultimately aims to include data from 500 gliomas, but already has shown the importance of a systematical approach and high sample numbers. Combining all detected homozygous deletions, focal amplifications and validated somatic nucleotide substitutions, they found three major pathways affected in a high percentage of glioblastomas: receptor tyrosine kinase signaling (altered in 88% of the GBMs), TP53 signaling (altered in 87%) and the pRB tumor suppressor pathway (altered in 78%). Novel genes in those pathways include the NF1 tumor suppressor gene and PIK3R1. Another large study on 22 GBMs sequenced all protein coding genes and performed copy number analysis and expression data analysis on these tumors [7]. All genes affected in more than two tumors were validated in a set of 80 GBMs. Besides confirmation of affected oncogenes and tumor suppressor genes in the formerly mentioned three pathways (50%, 64% and 68%, respectively) (see Scheme 1 and Table 1), they found the IDH1 gene to be mutated in 12% of the GBMs [7]. These mutations occurred in younger patients with mostly secondary GBMs and such tumors had a relatively favorable prognosis [7,8]. (For a more elaborate discussion on IDH1 see below).


Genetic alterations in glioma.

Bralten LB, French PJ - Cancers (Basel) (2011)

The three major pathways affected in a high percentage of glioblastomas and the most common genes affected in those pathways. Following the gene names, the percentages of genetic alterations found in glioblastoma are depicted.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756406&req=5

f1-cancers-03-01129: The three major pathways affected in a high percentage of glioblastomas and the most common genes affected in those pathways. Following the gene names, the percentages of genetic alterations found in glioblastoma are depicted.
Mentions: The Cancer Genome Atlas project has published mRNA expression data and DNA copy number alteration data of 206 GBMs and has sequenced >600 genes in 91 GBMs [6]. The project is still ongoing and ultimately aims to include data from 500 gliomas, but already has shown the importance of a systematical approach and high sample numbers. Combining all detected homozygous deletions, focal amplifications and validated somatic nucleotide substitutions, they found three major pathways affected in a high percentage of glioblastomas: receptor tyrosine kinase signaling (altered in 88% of the GBMs), TP53 signaling (altered in 87%) and the pRB tumor suppressor pathway (altered in 78%). Novel genes in those pathways include the NF1 tumor suppressor gene and PIK3R1. Another large study on 22 GBMs sequenced all protein coding genes and performed copy number analysis and expression data analysis on these tumors [7]. All genes affected in more than two tumors were validated in a set of 80 GBMs. Besides confirmation of affected oncogenes and tumor suppressor genes in the formerly mentioned three pathways (50%, 64% and 68%, respectively) (see Scheme 1 and Table 1), they found the IDH1 gene to be mutated in 12% of the GBMs [7]. These mutations occurred in younger patients with mostly secondary GBMs and such tumors had a relatively favorable prognosis [7,8]. (For a more elaborate discussion on IDH1 see below).

Bottom Line: Recently, two major studies have performed in-depth mutation analysis of glioblastomas (the most common and aggressive subtype of glioma).This systematic approach revealed three major pathways that are affected in glioblastomas: The receptor tyrosine kinase signaling pathway, the TP53 pathway and the pRB pathway.Exceptions include TP53 mutations and fusion genes involving the BRAF gene in astrocytic and pilocytic glioma subtypes, respectively.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Erasmus University Medical Center, Erasmus University Rotterdam, Dr Molewaterplein 50, 3000 CA, Rotterdam, the Netherlands. p.french@erasmusmc.nl.

ABSTRACT
Gliomas are the most common type of primary brain tumor and have a dismal prognosis. Understanding the genetic alterations that drive glioma formation and progression may help improve patient prognosis by identification of novel treatment targets. Recently, two major studies have performed in-depth mutation analysis of glioblastomas (the most common and aggressive subtype of glioma). This systematic approach revealed three major pathways that are affected in glioblastomas: The receptor tyrosine kinase signaling pathway, the TP53 pathway and the pRB pathway. Apart from frequent mutations in the IDH1/2 gene, much less is known about the causal genetic changes of grade II and III (anaplastic) gliomas. Exceptions include TP53 mutations and fusion genes involving the BRAF gene in astrocytic and pilocytic glioma subtypes, respectively. In this review, we provide an update on all common events involved in the initiation and/or progression across the different subtypes of glioma and provide future directions for research into the genetic changes.

No MeSH data available.


Related in: MedlinePlus