Table A1.
Main TKR mutations distributed by various types of solid and hematological tumors. [124,126,151,152,156,171,179,195,198,199,237,238,299,300,301,302].
| TKR Mutations | Most Representative Tumors | Other Described Alterations in Tumors |
|---|---|---|
| EGFR (primary mut.) Exon 19 (del), exon 21 (L858R, L861Q), exon 18 (G719X), exon 20 (ins) EGFR (secondary mut.) Exon 20 (T790M), D761Y, T854A, L747S |
NSCLC (15–20%) NSCLC |
Colorectal carcinoma (EGFR S464L, G465R, I491M, EGFR S492R) Pancreatic carcinoma Head and neck cancer (EGFR amplifications) Glioma (EGFR A289V, R108K, G598V, T263P) |
| HER2 mut. Exon 20 (ins) |
NSCLC (1–3%) | Breast cancer (HER2 amplification negative; HER2 D769Y, D769H, R896C, V777L, G309E, V842I, S310F, S310Y, C311R; HER2 inframe deletion (755-759), inframe insertion (780GSP), inframe insertion (781GSP) |
| ALK rearrangement EML4-ALK, KIF5B-ALK, KLC1-ALK, HIP1-ALK ALK (secondary mut.) Exon 23 (L1196M, S1206Y), exon 25 (G1269A), exon 22 (I1171T), V1180L, F1174L |
NSCLC (5–6%) NSCLC (5–6%) |
Anaplastic large cell lymphoma (other not ALK L1196M; ALK F856S, A348D) Glioblastoma (ALK fusions) Inflammatory myofibroblastic tumors (ALK C1156Y) Diffuse large B-cell lymphoma (ALK G1269A) Esophageal squamous cell carcinoma (ALK L1152R) Colorectal carcinoma (ALK F1245C) |
| FGFR1-4 | NSCLC (Squamous) (FGFR1 amplif., 17%) SCLC (FGFR1 amplif., 6%) Breast cancer (FGFR1 amplif., 15%) Cholangiocarcinoma (FGFR2 fusions) Urothelial carcinoma (FGFR2-3 fusions) Gastric cancer (FGFR2 amplif., 5–10%) |
Cholangiocarcinoma (other not FGFR2 fusion; FGFR2 N549H, V564F, K659M, L617V, K641R, R565A) Bladder cancer (oncogenic mutations others not FGFR3 fusions) Endometrial carcinoma (FGFR2 M536I, M538I, I548V, N550, E566G, L618M, K660E, S252W, N550K, V565I) NSCLC (Squamous) (other not FGFR1 amplification; FGFR2 W290C, S320C, K660; FGFR3 S249C, G691R) Myeloma multiple (FGFR3 K650, Y373C, V555M) |
| c-KIT mut. Exon 11, exon 9, exon 17, exon 13 |
GIST (80–85%) | AML (KIT D816V, N822K) Systemic mastocytosis (KIT D816V) Thymic carcinoma (KIT H697Y) Cutaneous melanoma (KIT amplif.) |
| PDGFR mut. Exon 18, exon 12, exon 14 |
GIST (6–8%) | Cutaneous melanoma (PDGFRA V658A, P577S, R841K, H845Y, G853D) Renal carcinoma (PDGFRA overexpression) Myelodisplasic syndrome (PDGFRA fusion) Dermatofibrosarcoma protuberans (translocation t(17:22)) |
| MET skipping mut. Exon 14 |
NSCLC (3%) | Renal carcinoma (MET H1112R) NSCLC (MET amplif.) Colorectal, gastric carcinoma (MET amplif.) |
| ROS1 | NSCLC, cholangiocarcinoma, gastric carcinoma (ROS1 fusions, 1–2%) | NSCLC (ROS1 G2032R) Inflammatory myofibroblastic tumor |
| RET | Papillary thyroid carcinoma (RET rearrangement, 5–40%) | MEN-2 syndrome, sporadic medullary thyroid carcinoma (RET mutations) |