Table 2.
PI3K/mTOR pathway alterations and other potentially actionable alterations identified in 20 osteosarcoma samples using the PHIAL algorithm
| Gene | Alterations | n | Sample ID | Molecularly targeted agent |
| PI3K/mTOR pathway alterations | ||||
| TSC2 | p.R611W, p.H593R | 2 | BZ04, BZ18 | PI3K/mTOR inhibitor |
| PTEN | p.E288*, p.P244fs | 2 | BZ04, BZ09 | PI3K/mTOR inhibitor |
| PTEN | Deleted | 5 | DF01, BZ03, SJD12, BZ06, SJD03 | PI3K/mTOR inhibitor |
| PIK3CA | p.E545D | 1 | DF01 | PI3K/mTOR inhibitor |
| AKT1 | p.T443M | 1 | BZ29 | AKT inhibitor |
| PIK3R1 | p.P84L | 1 | SJD13 | PI3K/mTOR inhibitor |
| PDPK1 | p.G530E | 1 | BZ21 | AKT inhibitor |
| EIF4B | p.R304K, p.R331K | 1 | SJD02 | None |
| NF1 | p.S2309fs | 1 | BZ14 | PI3K/mTOR inhibitor |
| NF1 | Deleted | 2 | BZ08, BZ21 | PI3K/mTOR inhibitor |
| NF2 | p.P170fs | 1 | BZ04 | PI3K/mTOR inhibitor |
| Growth factor receptor tyrosine kinases | ||||
| PDGFRA | Amplified | 1 | DF01 | Imatinib |
| PDGFRB | p.L803F | 1 | BZ19 | Imatinib |
| JAK1 | p.K245R, p.P548S | 2 | MX02, BZ11 | Jak inhibitor |
| ALK | p.K911T, p.A585T | 2 | BZ33, BZ03 | Crizotinib |
| KDR | p.S965R | 1 | BZ04 | Pan-tyrosine kinase inhibitor |
| FGFR4 | p.R171H | 1 | BZ30 | FGFR inhibitor |
| Other | ||||
| CDKN2A/B | Deleted | 2* | SJD12, BZ38 | CDK4/6 inhibitor |
| GSK3B | p.S9F | 1 | BZ11 | Wnt pathway inhibitor |
| ATM | Deleted | 1 | DF01 | PARP inhibitor |
| MYC | Amplified | 1 | DF01 | BET-bromodomain inhibitor |
*
Only samples with preserved RB1 counted, because CDK inhibitors do not function in the absence of RB1 protein.