Figure 3

Metastatic-specific RTK-RAS activating events in RAS/RAF wildtype tumors. In several tumors lacking KRAS, NRAS, or BRAF mutations, additional events in the RTK-RAS pathway were identified. (A) In patient 19, a metastatic-specific MAP2K1 p.Q56P mutation was identified. Transfection of GFP-tagged MAP2K1 plasmids demonstrate that the p.Q56P mutation hyperactivates downstream signaling to the same level as the known p.K57N mutation. (B) In patient 3, chromosome 7p is specifically amplified in the metastatic tumor. (C) FISH analysis confirms regions of high level amplification of EGFR in the metastatic tumor (right) while the primary tumor only shows 7p polysomy (left).