Figure 2

Retrospective analysis tests in silico predictions of gene mutations and sensitivity to EGFR family inhibitors. Associations reported in the Garnett study were tested in a blinded manner using our in silico model and predictions obtained were compared to results reported in the Garnett study. A, We created wild-type BRAF variants of four cancer cell lines – COLO205, HT29, MDAMB231 and U266 in silico and compared the effect of MEK1/2 inhibitor AZD2644 on these cell lines and on corresponding parent lines expressing mutant BRAF. Our data demonstrated that BRAF mutation increases sensitivity to AZD6244. B, We simulated three cell lines – H1650, H1975 and SW48 with wild-type or mutant BRAF and tested for sensitivity to the EGFR2 family kinase inhibitor, lapatinib. BRAF mutation decreases sensitivity of cells to lapatinib. C, Similarly, when four cell lines (AGS, H1437, MKN1 and MKN45) were tested for sensitivity to lapatinib, we observed that CDH1 mutation increases sensitivity to lapatinib. D, We generated cell lines with wild-type or MET over-expression and tested the effect of lapatinib (A549, AGS, H358 and HT29 cell lines). MET over-expression increases sensitivity to lapatinib.