PTENMutations and Activation of the PI3K/Akt/mTOR Signaling Pathway in Papillary Tumors of the Pineal Region
| Autor: | Torsten Pietsch, Tobias Goschzik, Dorota Denkhaus, Marco Gessi |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Adolescent Nerve Tissue Proteins medicine.disease_cause Pineal Gland Pathology and Forensic Medicine Young Adult Cellular and Molecular Neuroscience Exon medicine Humans PTEN Tensin Papillary tumors of the pineal region Protein kinase B PI3K/AKT/mTOR pathway Mutation biology Brain Neoplasms Point mutation Mucin-1 S100 Proteins PTEN Phosphohydrolase General Medicine Middle Aged medicine.disease Neoplasms Neuroepithelial Molecular biology Neurology biology.protein Keratins Female Neurology (clinical) Microtubule-Associated Proteins Pinealoma Signal Transduction |
| Zdroj: | Journal of Neuropathology & Experimental Neurology. 73:747-751 |
| ISSN: | 1554-6578 0022-3069 |
| DOI: | 10.1097/nen.0000000000000093 |
| Popis: | Papillary tumors of the pineal region (PTPR) are recognized as a distinct entity in the World Health Organization classification of CNS tumors. Papillary tumors of the pineal region frequently show loss of chromosome 10, but no studies have investigated possible target genes on this chromosome. Chromosome 10 harbors the PTEN (phosphatase and tensin homolog) gene, the inactivation of which, by mutation or epigenetic silencing, has been observed in different brain tumors, including high-grade gliomas. In this study, we investigated copy number changes by molecular inversion probe (MIP) analysis and the mutational status of PTEN in 13 PTPR by direct sequencing. MIP analysis of 5 PTPR showed chromosome 10 loss in all cases. In addition, there were losses of chromosomes 3, 14, 22, and X, and gains of whole chromosomes 8, 9, and 12 in more than 1 case. One case had a homozygous PTEN deletion; and 2 point mutations in exon 7 of PTEN (G251D and Q261stop) were found. Immunohistochemistry revealed decrease or loss of the PTEN protein and increased expression of p-Akt and p-S6. These results indicated that PTEN mutations and activation of the PI3K/Akt/mTOR signaling pathway may play a role in the biology of PTPR. This evidence may lead to the possible use of PI3K/Akt/mTOR inhibitors in therapy for patients with PTPR. |
| Databáze: | OpenAIRE |
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