Italiano, A., Chen, C. L., Thomas, R., Breen, M., Bonnet, F., Sevenet, N., Longy, M., Maki, R. G., Coindre, J. M., Antonescu, C. R. (December 2012) Alterations of the p53 and PIK3CA/AKT/mTOR pathways in angiosarcomas: a pattern distinct from other sarcomas with complex genomics. Cancer, 118 (23). pp. 5878-87. ISSN 1097-0142 (Electronic)0008-543X (Linking)
Abstract
BACKGROUND: The p53 and phosphoinositide-3-kinase, catalytic, alpha polypeptide/v-akt murine thymoma viral oncogene homolog/mechanistic target of rapamycin (PIK3CA/AKT/mTOR) pathways frequently are altered in sarcoma with complex genomics, such as leiomyosarcoma (LMS) or undifferentiated pleomorphic sarcoma (UPS). The scale of genetic abnormalities in these pathways remains unknown in angiosarcoma (AS). METHODS: The authors investigated the status of critical genes involved in the p53 and PIK3CA/AKT/mTOR pathways in a series of 62 AS. RESULTS: The mutation and deletion rates of tumor protein 53 (TP53) were 4% and 0%, respectively. Overexpression of p53 was detected by immunohistochemistry in 49% of patients and was associated with inferior disease-free survival. Although p14 inactivation or overexpression of the human murine double minute homolog (HDM2) were frequent in LMS and UPS and could substitute for TP53 mutation or deletion, such alterations were rare in angiosarcomas. Phosphorylated ribosomal protein S6 kinase (p-S6K) and/or phosphorylated eukaryotic translation initiation factor 4E binding protein 1 (p-4eBP1) overexpression was observed in 42% of patients, suggesting frequent activation of the PIK3CA/AKT/mTOR pathway in angiosarcomas. Activation was not related to intragenic deletion of phosphatase and tensin homolog (PTEN), an aberration that is frequent in LMS and UPS but absent in angiosarcomas. CONCLUSIONS: The current results indicated that angiosarcomas constitute a distinct subgroup among sarcomas with complex genomics. Although TP53 mutation and PTEN deletion are frequent in LMS and UPS, these aberrations are rarely involved in the pathogenesis of angiosarcoma.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Adult Aged Aged, 80 and over Female *Genes, p53 Genomics Hemangiosarcoma/etiology/*genetics Humans Male Middle Aged *Mutation PTEN Phosphohydrolase/genetics Phosphatidylinositol 3-Kinases/*physiology Proto-Oncogene Proteins B-raf/genetics Proto-Oncogene Proteins c-akt/*physiology Proto-Oncogene Proteins c-mdm2/analysis Signal Transduction/*physiology TOR Serine-Threonine Kinases/*physiology |
| Subjects: | bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > PTEN diseases & disorders > cancer > cancer types > angiosarcoma bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53 |
| CSHL Authors: | |
| Communities: | CSHL labs > Maki lab |
| Depositing User: | Matt Covey |
| Date: | 1 December 2012 |
| Date Deposited: | 20 Oct 2016 20:29 |
| Last Modified: | 20 Oct 2016 20:29 |
| PMCID: | PMC3434269 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/33732 |
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