Table 1.
Frequency of NTRK Receptor Transcript Fusions in TCGA (n = 9,966 adult tumor samples) and St Jude Pediatric Cancer Database (n = 3,501 pediatric tumor samples), and Specific Tumors With High Incidence of NTRK Fusions in the Literature
| No. of Tumors (%) | ||||||
|---|---|---|---|---|---|---|
| Tumor Sample | No. of Samples |
Any NTRK Fusion |
NTRK1 Fusion | NTRK2 Fusion | NTRK3 Fusion | |
| Adult tumors (TCGA)* | ||||||
| Total | 9,966 | 31 (0.31) | 9 (0.09) | 6 (0.06) | 16 (0.16) | |
| Thyroid cancer | 513 | 12 (2.34) | 5 (0.97) | — | 7 (1.36) | |
| Colon adenocarcinoma | 310 | 3 (0.97) | — | — | 3 (0.97) | |
| Low-grade glioma | 534 | 5 (0.94) | 1 (0.19) | 3 (0.56) | 1 (0.19) | |
| Sarcoma | 263 | 2 (0.76) | 2 (0.76) | — | — | |
| Glioblastoma multiforme | 180 | 1 (0.56) | 1 (0.56) | — | — | |
| Pancreatic adenocarcinoma | 179 | 1 (0002E56) | — | — | 1 (0.56) | |
| Head and neck SCC | 522 | 2 (0.38) | — | 1 (0.19) | 1 (0.19) | |
| Cervical cancer | 306 | 1 (0.33) | — | — | 1 (0.33) | |
| Melanoma | 476 | 1 (0.21) | — | — | 1 (0.21) | |
| Breast cancer | 1119 | 2 (0.18) | — | 1 (0.09) | 1 (0.09) | |
| Lung adenocarcinoma | 541 | 1 (0.18) | — | 1 (0.18) | — | |
| Pediatric tumors (St Jude PeCan)† | ||||||
| Total | 3,501 | 12 (0.34) | 5 (0.14) | 4 (0.11) | 3 (0.09) | |
| Melanoma | 9 | 1 (11.11) | 1 (11.11) | — | — | |
| High-grade glioma | 132 | 7 (5.3) | 4 (3.03) | 2 (1.52) | 1 (0.76) | |
| Low-grade glioma | 120 | 3 (2.5) | — | 2 (1.67) | 1 (0.83) | |
| B-cell ALL | 716 | 1 (0.14) | — | — | 1 (0.14) | |
| Illustrative Tumor Types With High Prevalence of NTRK Fusion | ||||||
| Tumor Type |
Reported Prevalence of NTRK Fusion (%) |
Comment | Reference | |||
| Mammary-analog secretory carcinoma of the salivary gland |
93–100 | ETV6-NTRK3 fusion | Skálová et al,14 | |||
| Skálová et al,15 | ||||||
| Bishop et al16 | ||||||
| Secretory breast carcinoma | 92 | ETV6-NTRK3 fusion | Tognon et al17 | |||
| Infantile congenital fibrosarcoma | 86–91 | ETV6-NTRK3 fusion | Bourgeois et al,18 | |||
| Orbach et al,19 | ||||||
| Rubin et al20 | ||||||
| Pediatric high-grade glioma | 40 | Fusions in NTRK1, NTRK2, or NTRK3 (in those age < 3 years) |
Wu et al21 | |||
Abbreviations: ALL, acute lymphoid leukemia; AML, acute myeloid leukemia; NTRK, neurotrophic-tropomyosin receptor tyrosine kinase; SCC, squamous cell carcinoma; TCGA, The Cancer Genome Atlas.
Adult tumor types exempt from NTRK fusions (22 tumor types): adrenocortical carcinoma (n = 79), bladder urothelial carcinoma (n = 414), cholangiocarcinoma (n = 36), B-cell lymphoma (n = 48), esophageal carcinoma (n = 185), renal chromophobe tumor (n = 66), renal clear cell carcinoma (n = 541), renal papillary cell carcinoma (n = 291), AML (n = 179), hepatocellular carcinoma (n = 374), lung squamous cell carcinoma (n = 502), mesothelioma (n = 87), ovarian serous carcinoma (n = 428), pheochromocytoma or paraganglioma (n = 184), prostate adenocarcinoma (n = 502), rectal adenocarcinoma (n = 95), gastric adenocarcinoma (n = 414), testicular germ cell tumors (n = 156), thymoma (n = 120), endometrial carcinoma (n = 185), uterine carcinosarcoma (n = 57), and uveal melanoma (n = 80).
Pediatric tumor types exempt from NTRK fusions (13 tumor types): T-cell ALL (n = 567), AML (n = 310), mixed leukemia (n = 26), medulloblastoma (n = 714), ependymoma (n = 92), choroid plexus carcinoma (n = 29), neuroblastoma (n = 382), Ewing sarcoma (n = 123), Wilms tumor (n = 91), rhabdomyosarcoma (n = 58), osteosarcoma (n = 53), adrenocortical carcinoma (n = 40), and retinoblastoma (n = 39).