Page 15 - Molecular features of low-grade developmental brain tumours
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GENERAL INTRODUCTION & OUTLINE OF THE THESIS
Figure 2. A schematic overview of the MAPK and mTOR pathways showing the proteins that are affected by mutations in TSC, GG, DNT and other pLGGs adapted from 224. IRS1, insulin receptor substrate 1; PI3K, PI3kinase; PDK1, phosphoinositide-dependent kinase-1; PTEN, phosphatase and tensin homologue; AKT, protein kinase B; GBR2, Growth factor receptor-bound protein 2; SOS, Son of Sevenless; RAF, RAF proto-oncogene serine/threonine-protein kinase; MEK, mitogen activated protein kinase; ERK, extracellular signal-regulated kinase; LKB1, tumour suppressor liver kinase B1; STRADĪ±, STE20-related kinase adaptor alpha; AMPK, AMP-activated protein kinase; TBC1D5, TBC1 Domain Family Member 5; RHEB, ras homolog enriched in brain; mTORC1, mammalian target of rapamycin complex 1; DEPDC5, DEP Domain Containing 5; NPRL2, NPR2 Like, GATOR1 Complex Subunit; NPRL3, NPR3 Like, GATOR1 Complex Subunit; GATOR1, Gap Activity Toward Rags 1; S6K1, p70S6kinase; S6, ribosomal S6
protein; 4EBP1, eIF4E-binding protein 1; eIF4E, binding of eukaryotic translation.
(characterised by abnormal morphology and orientation, an enlarged cell body and cytoplasmic accumulation of neurofilaments within the nucleus) and giant cells (characterised by an enlarged cell body, often multiple nuclei and eosinophilic cytoplasm) (Figure 3G- J) 74,78,79,81,83-86. Giant cells express both neuronal and glial markers, suggesting aberrant differentiation before cell migrate into the cortex 87-90 (for review see 70,91). Dysmorphic neurons are characterised by the expression of multiple cortical layer markers, independent of their laminar location and similar to that of cortical projection neurons, suggesting specific changes in a subgroup of intermediate progenitor cells 70,81,92. Moreover, the morphological features of dysmorphic neurons and giant cells can be explained by the enhanced activation
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