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• W2580794531 abstract "<b><i>Aim:</i></b> We aimed at exploring the activation pattern of the mTOR pathway in sporadic and hereditary pheochromocytomas (PCCs) and paragangliomas (PGLs). <b><i>Methods:</i></b> A total of 178 PCCs and 44 PGLs, already characterized for the presence of germline mutations in <i>VHL</i>, <i>RET</i>, <i>NF1</i>, <i>MAX</i>, <i>SDHA</i>, <i>SDHB</i>, <i>SDHC</i>, and <i>SDHD</i> as well as somatic mutations in <i>VHL</i>, <i>RET</i>, <i>H-RAS</i>, and <i>MAX</i>, were included in 5 tissue microarrays and tested using immunohistochemistry for mTOR and Rictor as well as the phosphorylated forms of mTOR, p70S6K, AMPK, AKT, 4EBP1, S6, and Raptor. <b><i>Results:</i></b> The positive correlation among most of the molecules investigated proved the functional activation of the mTOR pathway in PCCs/PGLs. Total mTOR, p-S6K and p-S6, and mTORC1-associated molecules p-Raptor and p-AMPK were all significantly overexpressed in PGLs rather than in PCCs, and in the head and neck rather than in abdominal locations. None of the markers, except for the low expression of p-mTOR, was associated with malignancy. Cluster 1 PCCs/PGLs had higher total mTOR, p-Raptor, and p-S6 expression than cluster 2 PCCs/PGLs. In contrast, p-mTOR and mTORC2-associated molecule Rictor were significantly overexpressed in cluster 2 tumors. Within cluster 1, molecules active in the mTORC1 complex were significantly overexpressed in <i>SDHX</i>- as compared to <i>VHL</i>-mutated tumors. <b><i>Conclusion:</i></b> In summary, the mTOR pathway is activated in a high proportion of PCCs/PGLs, with a preferential overactivation of the mTORC1 complex in PGLs of the head and neck and/or harboring <i>SDHX</i> mutations." @default.
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• W2580794531 date "2017-01-01" @default.
• W2580794531 modified "2023-10-18" @default.
• W2580794531 title "The mTORC1 Complex Is Significantly Overactivated in <b><i>SDHX</i></b>-Mutated Paragangliomas" @default.
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• W2580794531 doi "https://doi.org/10.1159/000455864" @default.
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