Supplemental Methods, Figures 1 - 8, Tables 1 - 2 from RAS/MAPK Activation Drives Resistance to Smo Inhibition, Metastasis, and Tumor Evolution in Shh Pathway–Dependent Tumors

Abstract

<p>Figure S1. Growth and survival of SMB cells depends on Shh signaling. Figure S2. SMB cell lines are a faithful model to study resistance to Smo inhibitors. Table S1. List of candidate genes with mutations used in the study. Figure S3. RAS signaling confers resistance to Smo inhibitor LDE225. Figure S4. FGF/RAS signaling abrogates dependence on Shh signaling. Figure S5. FGF/RAS-driven resistance to Smo inhibition is reversible and can be treated with MEK inhibitors. Figure S6. MEK inhibitors have therapeutic potential for HRAS SMB cells. Figure S7. Morphology of SMB(HRAS) cells differs from SMB parental cells. Figure S8. Immunohistochemistry of SFRP1, pERK and FGF in primary and metastatic samples from human Shh-subtype medulloblastoma patients. Table S2. Clinical diagnosis for human patient samples shown in Figure 5.</p>