Table 2 Sub-classification of potentially targetable somatic mutations for treatment planning
PIP ID | Diagnosis | Target alteration | Mutation (change) | Potential target therapy |
|---|---|---|---|---|
Tier 1 (Data demonstrating benefit- same tumor type, same gene) | ||||
 14-85546 | CML | BCR-ABL1 | Fusion | TKI |
 13-45348a | AML | IDH1 | c.394C > T (p.R132C) | IDH Inhibitor |
 14-24794a | AML | c-KIT; TET2; FLT3 | c.2446G > C (p.D816H); c.3663delT (p.C1221Wfs); c.2505 T > G (p.D835E) | TKI; Hypomethylating agent; TKI |
 14-53198 | AML | TET2 | c.1156G > T (p.V386L) | Hypomethylating agent |
 13-77086 | AML | c-KIT | c.1965 T > G (p.Asn655Lys) | TKIb |
Tier 2 (Data demonstrating benefit- different tumor type, same gene) | ||||
 15-18928 | Hepatic rhabdoid tumor | SMARCA4 | c.3574C > T (p.R1192C) | EZH2 Inhibitor |
 14-13487 | Osteosarcoma | TSC1 | c.2503-1G > C (p.?) | mTOR Inhibitor |
 14-47205 | Nephroblastomatosis | PIK3CA | c.1035 T > A (p.N345K) | PI3K/AKT/mTOR Inhibitor |
 15-40141 | Pleomorphic xanthoastrocytoma | TMEM106B-BRAF | Fusion | MEK Inhibitor |
Tier 3 (Published, presented, in press pre-clinical data demonstrating benefit- same tumor type, same gene) | ||||
 15-64793 | ALL | FOXP1-ABL1 | Fusion | TKIb |
 15-26188 | ALL | NUP214-ABL1 | Fusion | TKIb |
 15-79700 | ALL | NRAS | c.183A > T (p.Q61H) | MEK Inhibitor |
 14-20062 | ALL | KRAS | c.183A > T (p.Q61H) | MEK Inhibitor |
 14-24794a | AML | NRAS | c.183A > C (p.Q61H) | MEK Inhibitor |
 15-29224 | AML | JAK3 | c.1718C > T (p.A573V) | JAK Inhibitor |
 13-45348a | AML | NRAS | c.38G > C (p.G13A) | MEK Inhibitor |
 13-95124 | AML | NRAS; MLL-AFF1 (KMT2A-AFF1) | c.182A > G (p.Q61R); Fusion | MEK Inhibitor; DOT1L Inhibitor |
 14-45760 | AML | NRAS | c.38G > A (p.G13D) | MEK Inhibitor |
 13-50662 | AML | PTPN11 | c.1508G > T (p.G503V) | MEK Inhibitor |
 14-15491 | AML | NUP98-NSD1 | Fusion | DOT1L Inhibitor |
 14-27243 | Neuroblastoma | NRAS | c.181C > A (p.Q61K) | MEK Inhibitor |
 14-70449 | Rhabdomyosarcoma | NRAS | c.181C > A (p.Q61K) | MEK Inhibitor |
 14-42817 | Neuroblastoma | KRAS | c.34G > T (p.G12C) | MEK Inhibitor |
 15-11925a | Osteosarcoma | MYC | Overexpression | BET Inhibitor |
 16-74654 | Rhabdomyosarcoma | FGFR4 | c.1582G > T (p.G528C); c.1648G > C (p.V550L) | FGFR4 Inhibitor |
 15-23518 | Rhabdomyosarcoma | FGFR4 | c.1648G > C (p.V550L); c.1949G > T (p.R650L); Overexpression | FGFR4 Inhibitor |
 14-37237 | Glioblastoma multiforme | Gain 12q.14.1 involving CDK2 | Copy number | CDK4/6 Inhibitor |
 15-44470 | Medulloblastoma | PTCH1, SUFU, ZIC3 | Overexpression | SMO Inhibitor |
 15-10838 | Glioma | H3F3A; FGFR1 | c.83A > T (p.K28M); c.1731C > A (p.N577K) | HDAC Inhibitor |
 15-27992 | Hepatic rhabdoid tumor | Homozygous deletion of chr 22q11.23 with homozygous deletion of SMARCB1; Loss of expression of SMARCB1 | Copy number; Loss of expression with biallelic deletion | EZH2 Inhibitor |
Tier 4 (Published, presented, in press pre-clinical data demonstrating benefit- different tumor type, same gene) | ||||
 15-36388 | AML | MLL3 (KMT2C) | c.2110G > T (p.E704X) | BET Inhibitor |
 13-72282 | T-ALL | KRAS; JAK1; STAT5B | c.40G > A (p.V14I); c.3076A > G (p.K1026E); c.2110A > C (p.I704L) | MEK Inhibitor; JAK Inhibitor; BCL2/BCLX-L Inhibitor |
 15-66870 | Adrenocortical carcinoma | ALK | c.3436C > A (p.Q1146K) | ALK Inhibitorb |
Tier 5 (Anything else the molecular tumor board thought was sufficient to qualify for treatment planning) | ||||
 15-16072 | ALL | SMARCC2-PDGFRB | Fusion | TKI |
 14-75899 | Neuroblastoma | CDK4, MDM2 | Overexpression | NEPENTHE trial [NCT02780128] |
 15-11925a | Osteosarcoma | MCL1, CCNE1 | Overexpression | CDK4/6 Inhibitor |
 15-35162 | Osteosarcoma | CUL4A | Overexpression | NAE Inhibitor |
 14-71727 | Osteosarcoma | RAD51C | c.24 T > G (p.F8L) | PARP Inhibitor |
 15-83826 | Osteosarcoma | PDGFRA, KDR (VEGFR2) | Overexpression | MTKIb |
 13-21968 | Congenital fibrosarcoma | EML4-NTRK3 | Fusion | ALK Inhibitor |
 14-84044 | Inflammatory myofibroblastic tumor | VCAN-IL23R | Fusion | JAK Inhibitorb |