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Cell lineStatus FGFR1 DMS-114Gene amplification NCI-H520Gene amplification NCI-H1581Gene amplification FGFR2 NCI-H716Gene amplification KATO-IIIGene amplification.

Published byBrent Lawson Modified over 8 years ago

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Presentation on theme: "Cell lineStatus FGFR1 DMS-114Gene amplification NCI-H520Gene amplification NCI-H1581Gene amplification FGFR2 NCI-H716Gene amplification KATO-IIIGene amplification."— Presentation transcript:

1 Cell lineStatus FGFR1 DMS-114Gene amplification NCI-H520Gene amplification NCI-H1581Gene amplification FGFR2 NCI-H716Gene amplification KATO-IIIGene amplification HSC-39Gene amplification SNU-16Gene amplification SUM-52PEGene amplification MFE-280Gene mutation (S252W) MFE-296Gene mutation (N549K) AN 3CAGene mutation (K310R/N549K) FGFR3 KMS-11 Gene mutation (Y373C), t(4;14) translocation UM-UC-14Gene mutation (S249C) RT-4 Gene rearrangement (FGFR3-TACC3) Others NCI-N87Wild type (ERBB2 amplification) MKN-45Wild type (c-Met amplification) SK-MEL-1Wild type (BRAF V600E) MeWoWild type (NF1 loss) HCT-116Wild type (KRAS G13D) Supplementary Table S1. Supplementary Table S1 Genetic status information of cancer cell lines

2 Supplementary Table S2. Supplementary Table S2 List of probe that is significantly modulated by CH5183284/Debio 1347 PROBE_IDSYMBOLLog2 ratioLog10 p-value 215728_s_atACOT7-1.04-2.83 220223_atATAD5-1.06-3.71 202769_atCCNG21.72-3.26 204695_atCDC25A-1.56-4.02 203968_s_atCDC6-1.74-4.27 218726_atDKFZp762E1312-1.04-4.21 218585_s_atDTL-1.49-3.93 208892_s_atDUSP6-5.08-2.58 208891_atDUSP6-4.94-2.56 218488_atEIF2B3-1.15-3.44 204768_s_atFEN1-1.55-4.10 204767_s_atFEN1-1.42-4.49 203023_atHSPC111-1.35-3.31 201631_s_atIER3-1.33-1.98 209100_atIFRD2-1.40-3.44 218305_atIPO4-1.05-2.30 203882_atISGF3G1.07-2.30 36711_atMAFF-1.70-1.98 220651_s_atMCM10-2.25-5.04 202107_s_atMCM2-1.12-3.00 201555_atMCM3-1.06-3.56 216237_s_atMCM5-1.16-4.04 210983_s_atMCM7-1.29-2.97 208795_s_atMCM7-1.27-3.46 212789_atNCAPD3-1.03-4.21 212949_atNCAPH-1.46-4.92 219031_s_atNIP7-1.02-2.63 218889_atNOC3L-1.05-3.43 201695_s_atNP-1.08-1.44 219105_x_atORC6L-1.15-4.18 201014_s_atPAICS-1.02-4.13 219148_atPBK-1.03-2.69 217996_atPHLDA1-1.39-2.22 209803_s_atPHLDA2-1.54-1.47 203622_s_atPNO1-1.19-3.15 205909_atPOLE2-1.36-2.61 206653_atPOLR3G-1.23-1.74 218866_s_atPOLR3K-1.29-3.04 1053_atRFC2-1.17-3.04 204128_s_atRFC3-1.43-2.81 204127_atRFC3-1.17-3.21 201890_atRRM2-1.69-3.99 219037_atRRP15-3.30 219493_atSHCBP1-1.24-3.26 201920_atSLC20A1-1.19-3.05 221020_s_atSLC25A32-1.06-3.19 219911_s_atSLCO4A1-1.77-2.53 218145_atTRIB3-1.69-2.26 204033_atTRIP13-1.41-3.12 213334_x_atUCHL5IP-1.19-2.30 209825_s_atUCK2-1.25-2.08

3 Supplementary Table S3. Supplementary Table S3 In vivo efficacy data of CH5183284/Debio 1347 Xenograft model FGFR genetic alteration status Tumor growth inhibition (%) CH5183284/Debio 1347 (100 mg/kg) DMS-114 FGFR2 gene amplification 94% SNU-16 FGFR2 gene amplification 147% NCI-N87 Wild type (ERBB2 amplification) -1% MKN-45 Wild type (c-Met amplification) -13%

4 Supplementary Figure S1. Supplementary Figure S1. MAPK pathway suppression by CH5183284/Debio 1347 in FGFR genetically altered cancer cell lines A MEK-inducible gene signature was obtained from the work from Pratilas et al. From their list for 60 differentially expressed probes upon MEK inhibitor treatment, 56 down-regulated probes were used. Distributions of log-ratio to control were plotted as a histogram. X- axis represents log-ratio. Y-axis represents frequency. Distribution pattern for probes in the MEK-inducible signature were colored in blue, and distribution for other probes were in red. Cells were treated with 1 µM of CH5183284/Debio 1347 or DMSO for 24-h. Total RNA samples from the cells were analyzed with microarray. FGFR2 altered cancers FGFR1 altered cancersFGFR3 altered cancersFGFR wild type NCI-H716 (Amplification) KATO-III (Amplification) HSC-39 (Amplification) DMS-114 (Amplification) NCI-H520 (Amplification) NCI-H1581 (Amplification) KMS-11 (Mutation) UM-UC-14 (Mutation) RT-4 (Fusion) NCI-N87 x Log-ratio Frequency y MFE-280 (Mutation) MFE-296 (Mutation) AN3 CA (Mutation) SNU-16 (Amplification)

5 Supplementary Figure S2. DUSP6: 208891_at A

6 Supplementary Figure S2 (Cont.). DUSP6: 208892_s_at B

7 Supplementary Figure S2 (Cont.) DUSP6: 208893_at Supplementary Figure S2. Modulation of DUSP6 expression in FGFR inhibitor sensitive cancer cell lines Bar graphs shows ratio in signal of probes (a. 208891_at, b. 208892_s_at, c. 208893_at) that recognize DUSP6 compared with the treatment of DMSO in 14 cancer cell lines. Y-axis represents signal intensity. C

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