Personalized Management of Pheochromocytoma and Paraganglioma

. 2021 Jun 19;43(2):199–239. doi: 10.1210/endrev/bnab019

Practical tip/synthesis:
• Figure 5 summarizes the kinase signaling pathway–associated cluster 2 with all its loss- and gain-of-function mutations. • Cluster 2 comprises mutations in the following genes associated with tyrosine kinase signaling: RET, NF1, HRAS, TMEM127, MAX, FGFR1, and rare cases with Met, MERTK, BRAF, and NGFR. • These mutations lead to activation of tyrosine kinase-associated signaling pathways, such as PI3K/AKT, RAS/RAF/ERK, and mTORC1, and finally as a common intersection point with cluster 1 to increased synthesis of HIF-α and, among other changes, to enhanced cell growth, cell survival, and tumor formation.

Practical tip/synthesis:

• Figure 5 summarizes the kinase signaling pathway–associated cluster 2 with all its loss- and gain-of-function mutations.
• Cluster 2 comprises mutations in the following genes associated with tyrosine kinase signaling: RET, NF1, HRAS, TMEM127, MAX, FGFR1, and rare cases with Met, MERTK, BRAF, and NGFR.
• These mutations lead to activation of tyrosine kinase-associated signaling pathways, such as PI3K/AKT, RAS/RAF/ERK, and mTORC1, and finally as a common intersection point with cluster 1 to increased synthesis of HIF-α and, among other changes, to enhanced cell growth, cell survival, and tumor formation.