Limits...
Molecular neuropathology of gliomas.

Riemenschneider MJ, Reifenberger G - Int J Mol Sci (2009)

Bottom Line: Gliomas are the most common primary human brain tumors.They comprise a heterogeneous group of benign and malignant neoplasms that are histologically classified according to the World Health Organization (WHO) classification of tumors of the nervous system.In fact, first steps have been undertaken in supplementing classical histopathological diagnosis by the use of molecular tests, such as MGMT promoter hypermethylation in glioblastomas or detection of losses of chromosome arms 1p and 19q in oligodendroglial tumors.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuropathology, Heinrich-Heine-University, Duesseldorf, Germany. m.j.riemenschneider@gmx.de

ABSTRACT
Gliomas are the most common primary human brain tumors. They comprise a heterogeneous group of benign and malignant neoplasms that are histologically classified according to the World Health Organization (WHO) classification of tumors of the nervous system. Over the past 20 years the cytogenetic and molecular genetic alterations associated with glioma formation and progression have been intensely studied and genetic profiles as additional aids to the definition of brain tumors have been incorporated in the WHO classification. In fact, first steps have been undertaken in supplementing classical histopathological diagnosis by the use of molecular tests, such as MGMT promoter hypermethylation in glioblastomas or detection of losses of chromosome arms 1p and 19q in oligodendroglial tumors. The tremendous progress that has been made in the use of array-based profiling techniques will likely contribute to a further molecular refinement of glioma classification and lead to the identification of glioma core pathways that can be specifically targeted by more individualized glioma therapies.

Show MeSH

Related in: MedlinePlus

Core pathways involved in the pathogenesis of gliomas.Note the interrelationships between p53, RB, growth factor receptor, PTEN/PI3K/AKT and RAS signaling on the regulation of cell proliferation and apoptosis. While TP53 mutation, amplification of MDM2/MDM4 or p14ARF deletion/methylation inhibits apoptosis, alterations in p16INK4a, p15INK4b, p18INK4c and p21waf1 disinhibit cell cycle progression at the G1/S-phase checkpoint via cyclin-dependent kinases by phosphorylation of RB1 and release of E2F transcription factors. Amplification, overexpression or mutation of growth factor receptors stimulates cell proliferation and inhibits apoptosis through both the RAS as well as the PI3K/AKT signaling pathway. The RAS signaling pathway can be alternatively activated by mutations in the NF1, the PI3K/AKT signaling pathway by mutations in the PTEN gene and less commonly, the PIK3CA or the PIK3R1 gene.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2662467&req=5

f6-ijms-10-00184: Core pathways involved in the pathogenesis of gliomas.Note the interrelationships between p53, RB, growth factor receptor, PTEN/PI3K/AKT and RAS signaling on the regulation of cell proliferation and apoptosis. While TP53 mutation, amplification of MDM2/MDM4 or p14ARF deletion/methylation inhibits apoptosis, alterations in p16INK4a, p15INK4b, p18INK4c and p21waf1 disinhibit cell cycle progression at the G1/S-phase checkpoint via cyclin-dependent kinases by phosphorylation of RB1 and release of E2F transcription factors. Amplification, overexpression or mutation of growth factor receptors stimulates cell proliferation and inhibits apoptosis through both the RAS as well as the PI3K/AKT signaling pathway. The RAS signaling pathway can be alternatively activated by mutations in the NF1, the PI3K/AKT signaling pathway by mutations in the PTEN gene and less commonly, the PIK3CA or the PIK3R1 gene.

Mentions: Recent milestones are the publications of two large-scale multi-dimensional studies, one by Johns Hopkins researchers in Science [10], the other by The Cancer Genome Atlas Research Network in Nature [124]. Parsons and colleagues investigated 22 human glioblastoma samples for genome-wide DNA copy number and gene expression aberrations as well as somatic mutations in 20,661 protein coding genes. In addition to the identification of yet unknown IDH1 mutations, integrative data analysis identified a set of glioblastoma candidiate cancer genes that mainly functioned within the TP53, RB1 and PI3K/PTEN signaling pathways [10] (Figure 6).


Molecular neuropathology of gliomas.

Riemenschneider MJ, Reifenberger G - Int J Mol Sci (2009)

Core pathways involved in the pathogenesis of gliomas.Note the interrelationships between p53, RB, growth factor receptor, PTEN/PI3K/AKT and RAS signaling on the regulation of cell proliferation and apoptosis. While TP53 mutation, amplification of MDM2/MDM4 or p14ARF deletion/methylation inhibits apoptosis, alterations in p16INK4a, p15INK4b, p18INK4c and p21waf1 disinhibit cell cycle progression at the G1/S-phase checkpoint via cyclin-dependent kinases by phosphorylation of RB1 and release of E2F transcription factors. Amplification, overexpression or mutation of growth factor receptors stimulates cell proliferation and inhibits apoptosis through both the RAS as well as the PI3K/AKT signaling pathway. The RAS signaling pathway can be alternatively activated by mutations in the NF1, the PI3K/AKT signaling pathway by mutations in the PTEN gene and less commonly, the PIK3CA or the PIK3R1 gene.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2662467&req=5

f6-ijms-10-00184: Core pathways involved in the pathogenesis of gliomas.Note the interrelationships between p53, RB, growth factor receptor, PTEN/PI3K/AKT and RAS signaling on the regulation of cell proliferation and apoptosis. While TP53 mutation, amplification of MDM2/MDM4 or p14ARF deletion/methylation inhibits apoptosis, alterations in p16INK4a, p15INK4b, p18INK4c and p21waf1 disinhibit cell cycle progression at the G1/S-phase checkpoint via cyclin-dependent kinases by phosphorylation of RB1 and release of E2F transcription factors. Amplification, overexpression or mutation of growth factor receptors stimulates cell proliferation and inhibits apoptosis through both the RAS as well as the PI3K/AKT signaling pathway. The RAS signaling pathway can be alternatively activated by mutations in the NF1, the PI3K/AKT signaling pathway by mutations in the PTEN gene and less commonly, the PIK3CA or the PIK3R1 gene.
Mentions: Recent milestones are the publications of two large-scale multi-dimensional studies, one by Johns Hopkins researchers in Science [10], the other by The Cancer Genome Atlas Research Network in Nature [124]. Parsons and colleagues investigated 22 human glioblastoma samples for genome-wide DNA copy number and gene expression aberrations as well as somatic mutations in 20,661 protein coding genes. In addition to the identification of yet unknown IDH1 mutations, integrative data analysis identified a set of glioblastoma candidiate cancer genes that mainly functioned within the TP53, RB1 and PI3K/PTEN signaling pathways [10] (Figure 6).

Bottom Line: Gliomas are the most common primary human brain tumors.They comprise a heterogeneous group of benign and malignant neoplasms that are histologically classified according to the World Health Organization (WHO) classification of tumors of the nervous system.In fact, first steps have been undertaken in supplementing classical histopathological diagnosis by the use of molecular tests, such as MGMT promoter hypermethylation in glioblastomas or detection of losses of chromosome arms 1p and 19q in oligodendroglial tumors.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuropathology, Heinrich-Heine-University, Duesseldorf, Germany. m.j.riemenschneider@gmx.de

ABSTRACT
Gliomas are the most common primary human brain tumors. They comprise a heterogeneous group of benign and malignant neoplasms that are histologically classified according to the World Health Organization (WHO) classification of tumors of the nervous system. Over the past 20 years the cytogenetic and molecular genetic alterations associated with glioma formation and progression have been intensely studied and genetic profiles as additional aids to the definition of brain tumors have been incorporated in the WHO classification. In fact, first steps have been undertaken in supplementing classical histopathological diagnosis by the use of molecular tests, such as MGMT promoter hypermethylation in glioblastomas or detection of losses of chromosome arms 1p and 19q in oligodendroglial tumors. The tremendous progress that has been made in the use of array-based profiling techniques will likely contribute to a further molecular refinement of glioma classification and lead to the identification of glioma core pathways that can be specifically targeted by more individualized glioma therapies.

Show MeSH
Related in: MedlinePlus