Table 1.
Molecular alteration | Gene | Molecular subtypes | Methods of detection | Frequency (%) | Therapy |
---|---|---|---|---|---|
Mutation | EGFR epidermal growth factor receptor |
Exon 19 deletion and exon 21 L858 | Direct sequencing, Real-time PCR, NGS |
C 12-−27 EA 50–60 |
Gefitinib, Erlotinib, Afatinib, Osimertinib, Dacomitinib |
Exon 20 T790M | 60 | Osimertinib | |||
Exon 20 insertion | 2.5 | Poziotinib | |||
KRAS Kirsten rat sarcoma viral oncogene homolog |
G12X, G13X | C-32 EA-2 |
MEK Inhibitors | ||
BRAF | V600E | 2 | Dabrafenib, Vemurafenib | ||
MET | Exon 14 splice mutation | 3 | Crizotinib, Cabozantinib, Capmatinib | ||
FGFR3 | S249C | 5.5 | FGFR Inhibitors | ||
HER2 | Exon 20 | 1 | Afatinib, Trastuzumab, Dacomitinib | ||
Translocation | ALK anaplastic lymphoma kinase | EML-4-ALK, TGT-ALK, KIF5B-ALK | FISH, IHC, NGS | 5–7 | Crizotinib, Ceritinib, Alectinib, Brigatinib, Lorlatinib |
ROS1 c-ros oncogene 1 |
CD74-ROS1, SLC34A2-ROS1, EXR- ROS1, SDC4-ROS1 | FISH, NGS | 3.4 | Crizotinib, Ceritinib, Lorlatinib | |
RET rearranged during transfection |
CCDC6-RET, KIF5B-RET | 1 | Cabozantinib, Vandetanib, Lenvatinib, Alectinib, Ponatinib | ||
NTRK neurotropic tropomyosin receptor kinase | TPM3-NTRK, CD74-NTRK, MPRIP-NTRK | 0.1 | Entrectinib, Larotrectinib | ||
FGFR3 fibroblast growth factor receptor | FGFR3-TACC, BAG4-FGFR1 | 0.5–2 | FGFR Inhibitors | ||
Ampification | MET | IHC, NGS, FISH, real-time PCR | 3–5 | Crizotinib FGFR Inhibitors |
|
HER2 | FISH, NGS, real-time PCR |
13 | Afatinib, Trastuzumab |
ADC, adenocarcinoma; C, Caucasian; EA, East Asians; FISH, fluorescence in situ hybridization; IHC, immunohistochemistry; NGS, next generation sequencing.