G2Cdb::Human Disease report

Disease id
D00000072
Name
Glioblastoma
Nervous system disease
yes

Genes (1)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00001624 PIK3CA
phosphoinositide-3-kinase, catalytic, alpha polypeptide
Y (15924252) No mutation found (N) N
G00001624 PIK3CA
phosphoinositide-3-kinase, catalytic, alpha polypeptide
Y (16150119) Unknown (?) Y
G00001624 PIK3CA
phosphoinositide-3-kinase, catalytic, alpha polypeptide
Y (17235514) Microinsertion (MI) Y

References

  • PIK3CA alterations in primary (de novo) and secondary glioblastomas.

    Kita D, Yonekawa Y, Weller M and Ohgaki H

    International Agency for Research on Cancer, 150 cours Albert Thomas, 69372, Lyon Cedex 08, France.

    We assessed alterations in the EGFR/PTEN/PI3K pathway in 107 primary (de novo) glioblastomas and 32 secondary glioblastomas that progressed from low-grade or anaplastic astrocytomas. SSCP followed by DNA sequencing in exons 9 and 20 of the PIK3CA gene revealed missense mutations in 5/107 (5%) primary and 1/32 (3%) secondary glioblastomas. Quantitative real-time PCR showed PIK3CA amplification (>3 copy numbers) in 14/107 (13%) primary and 3/32 (9%) secondary glioblastomas. Only one glioblastoma showed both PIK3CA mutation and amplification. Taken together with previously published data on EGFR amplification and PTEN mutations, at least one alteration in the EGFR, PTEN, or PIK3CA genes was detected in 63% of primary glioblastomas, which was significantly more frequent than in secondary glioblastomas (31%; P < 0.001). Furthermore, this signaling pathway was altered by either PTEN mutations or PIK3CA amplification in 10 of 12 (83%) malignant glioma cell lines analyzed. These results suggest that the EGFR/PTEN/PI3K pathway is frequently altered in glioblastomas and is a promising target for therapy, in particular for primary glioblastomas.

    Acta neuropathologica 2007;113;3;295-302

  • Genetic alteration and expression of the phosphoinositol-3-kinase/Akt pathway genes PIK3CA and PIKE in human glioblastomas.

    Knobbe CB, Trampe-Kieslich A and Reifenberger G

    Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany.

    Glioblastomas frequently carry genetic alterations resulting in an aberrant activation of the phosphoinositol-3-kinase (Pi3k)/protein kinase B (Akt) signalling pathway, including most notably phosphatase and tensin homolog (PTEN) mutation, epidermal growth factor receptor (EGFR) amplification and rearrangement, as well as carboxyl-terminal modulator protein (CTMP) hypermethylation [Knobbe et al., (2004) Hypermethylation and transcriptional downregulation of the carboxyl-terminal modulator protein gene in glioblastomas. J Natl Cancer Institute, 96, 483-486]. Here, we investigated two further Pi3k/Akt pathway genes, namely PIK3CA (3q26.3) and phosphatidylinositol-3-kinase enhancer (PIKE) (CENTG1, 12q14), for genetic alteration and aberrant expression in a series of 97 primary glioblastomas. Single strand conformation polymorphism (SSCP) analysis of PIK3CA revealed somatic mutations in five tumours (5%). Twelve glioblastomas (12%) showed amplification of PIKE with invariable co-amplification of the adjacent CDK4 gene. All tumours with PIKE amplification as well as the vast majority of glioblastomas without amplification demonstrated increased expression of PIKE-A but not PIKE-S/L transcripts as compared with non-neoplastic brain tissue. Taken together, our data support an important role of PIK3CA and PIKE gene aberrations in the molecular pathogenesis of primary glioblastomas.

    Neuropathology and applied neurobiology 2005;31;5;486-90

  • Mutations of the PIK3CA gene are rare in human glioblastoma.

    Mueller W, Mizoguchi M, Silen E, D'Amore K, Nutt CL and Louis DN

    Acta neuropathologica 2005;109;6;654-5

Literature (3)

Pubmed - human_disease

  • PIK3CA alterations in primary (de novo) and secondary glioblastomas.

    Kita D, Yonekawa Y, Weller M and Ohgaki H

    International Agency for Research on Cancer, 150 cours Albert Thomas, 69372, Lyon Cedex 08, France.

    We assessed alterations in the EGFR/PTEN/PI3K pathway in 107 primary (de novo) glioblastomas and 32 secondary glioblastomas that progressed from low-grade or anaplastic astrocytomas. SSCP followed by DNA sequencing in exons 9 and 20 of the PIK3CA gene revealed missense mutations in 5/107 (5%) primary and 1/32 (3%) secondary glioblastomas. Quantitative real-time PCR showed PIK3CA amplification (>3 copy numbers) in 14/107 (13%) primary and 3/32 (9%) secondary glioblastomas. Only one glioblastoma showed both PIK3CA mutation and amplification. Taken together with previously published data on EGFR amplification and PTEN mutations, at least one alteration in the EGFR, PTEN, or PIK3CA genes was detected in 63% of primary glioblastomas, which was significantly more frequent than in secondary glioblastomas (31%; P < 0.001). Furthermore, this signaling pathway was altered by either PTEN mutations or PIK3CA amplification in 10 of 12 (83%) malignant glioma cell lines analyzed. These results suggest that the EGFR/PTEN/PI3K pathway is frequently altered in glioblastomas and is a promising target for therapy, in particular for primary glioblastomas.

    Acta neuropathologica 2007;113;3;295-302

  • Mutations of the PIK3CA gene are rare in human glioblastoma.

    Mueller W, Mizoguchi M, Silen E, D'Amore K, Nutt CL and Louis DN

    Acta neuropathologica 2005;109;6;654-5

Pubmed - other

  • Genetic alteration and expression of the phosphoinositol-3-kinase/Akt pathway genes PIK3CA and PIKE in human glioblastomas.

    Knobbe CB, Trampe-Kieslich A and Reifenberger G

    Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany.

    Glioblastomas frequently carry genetic alterations resulting in an aberrant activation of the phosphoinositol-3-kinase (Pi3k)/protein kinase B (Akt) signalling pathway, including most notably phosphatase and tensin homolog (PTEN) mutation, epidermal growth factor receptor (EGFR) amplification and rearrangement, as well as carboxyl-terminal modulator protein (CTMP) hypermethylation [Knobbe et al., (2004) Hypermethylation and transcriptional downregulation of the carboxyl-terminal modulator protein gene in glioblastomas. J Natl Cancer Institute, 96, 483-486]. Here, we investigated two further Pi3k/Akt pathway genes, namely PIK3CA (3q26.3) and phosphatidylinositol-3-kinase enhancer (PIKE) (CENTG1, 12q14), for genetic alteration and aberrant expression in a series of 97 primary glioblastomas. Single strand conformation polymorphism (SSCP) analysis of PIK3CA revealed somatic mutations in five tumours (5%). Twelve glioblastomas (12%) showed amplification of PIKE with invariable co-amplification of the adjacent CDK4 gene. All tumours with PIKE amplification as well as the vast majority of glioblastomas without amplification demonstrated increased expression of PIKE-A but not PIKE-S/L transcripts as compared with non-neoplastic brain tissue. Taken together, our data support an important role of PIK3CA and PIKE gene aberrations in the molecular pathogenesis of primary glioblastomas.

    Neuropathology and applied neurobiology 2005;31;5;486-90

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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