Table 2.
Actionable somatic genome variants in cancer cells and associated medications1
| Genetic Abnormality2 | HGVS Nomenclature3 | Target4 | Medications | Disease5 |
|---|---|---|---|---|
| AKT Mut (Act) | p.Glu17Lys | mTOR | sirolimus, everolimus | RCC |
| BCR-ABL (SV) | t(9;22) (q34.1;q11.21) | ABL | imatinib, dasatinib | CML, Ph+ ALL |
| BCR-ABL (SV + Mut) | p.Val299Leu | ABL | bosutinib, nilotinib | imatinib resistant CML |
| BCR-ABL (T135I) | p.Thr135Ile | ABL | ponatinib | CML, Ph+ ALL |
| BCR-ABL (SV) | t(9;22) (q34.1;q11.21) | SRC | dasatinib | CML, Ph+ ALL |
| BRCA1/2 variants | too numerous to list | PARP | olaparib | ovarian |
| BRAF SNVs (V600E/K) | p.Val600Glu, p.Val600Lys, p.Val600Asp | BRAF | dabrafenib, vemurafenib | melanoma |
| BRAF SNVs (V600) | p.Val600Glu, p.Val600Lys, p.Val600Asp | MEK | trametinib | melanoma |
| EGFR (Ex 19 del., SNV L858R) | p.Glu746_Ala750del, p.Leu858Arg | EGFR | afatinib, erlotinib | NSCLC (EGRF+) |
| EGFR Mut (Act, Amp) | p.Glu746_Ala750del, p.Leu858Arg | EGFR | gefitinib | NSCLC (EGRF+) |
| EGFR+ & WT KRAS | NA | EGFR | cetuximab, panitumumab | EGRF+ colon (WT KRAS) |
| EML-ALK (SV) | inv(2)(p21p23) | ALK | crizotinib | NSCLC |
| FLT3 CNV (Amp) | p.D600_L601insFREYEYD, p.Asp835Tyr | FTL3 | sunitinib, sorafenib | AML |
| HER2 (Amp) | NA | ERBB2 | lapatinib, trastuzumab | HER2+ breast |
| KIT (Act Mut) | p.Trp557_Lys558del, p.Asp579del, p.Val559Asp | KIT | imatinib, sunitinib | RCC, GIST |
| PDGFR (Mut, SV) | p.Asp842Val | PDGFR | sunitinib, imatinib | RCC, GIST, pancreas |
| PI3K (Mut, Amp) | PIK3CA p.Glu542Lys, p.Glu545Lys; p.His1047Arg, p.His1047Leu | PI3K | idelalisib | CLL, NHL |
| RARA (SV, gene fusion) | t(15;17)(q24;q21) | RARA | tretinoin, alitretinoin | APL CTCL, Kaposi |
| RARA (SV, gene fusion) | t(15;17)(q24;q21) | RARA | arsenic trioxide | APL |
| SMO (Mut, Act) | p.Trp535Leu, p.Arg199Trp, p.Arg562Gln | Smoothen | vismodegib | basal cell |
| VHL (Mut) | too numerous to list | VEGFR | sorafenib | RCC, hepatic, thyroid |
| VEGF (Mut) | NA | VEGF | ziv-aflibercept | colon |
Medications targeting normal cell surface proteins that are expressed on some tumor cells (e.g., ER, PR, CD20, CD30, CD52) are not included in this summary of drugs targeting proteins with aberrant expression or function due to somatic genome variants.
Act= activating; Amp= amplification, typically by CNV; CNV=copy number variant; Epigen= epigenetic; Mut=mutation; NA = not applicable; SNV= single nucleotide variant; SV= structural variant.
Only representative examples of known mutations are shown.
Targets are generally protein products encoded by the gene listed.
ALCL= anaplastic large cell lymphoma; ALL= acute lymphoblastic leukemia; AML= acute myeloid leukemia; CLL=chronic myeloid leukemia, CML= chronic myeloid leukemia; CTCL= cutaneous T-cell lymphoma; Ex= exon; GIST= gastrointestinal stromal tumor; NHL= non-Hodgkins lymphoma; NSCLC= non-small cell lung cancer; RCC= renal cell carcinoma.