NTRK tumour epidemiology
Lung cancer is the second most common cancer type (excluding skin cancer). The majority of cases (around 84%) are non-small cell lung cancer (NSCLC), while about 13% are small cell lung cancer [1]. In 2020, the International Agency for Research on Cancer estimated the worldwide incidence of lung cancer to be 2,206,771 cases with 1,796,144 deaths and a 5-year prevalence of 2,604,791 [1].
Prevalence of NTRK fusion
NTRK1 gene rearrangements in NSCLC were first described in 2013 among a subset of patients with NSCLC with adenocarcinoma histology and no detectable EGFR, KRAS, ALK, or ROS1 alterations (3/91; 3.3%) [2]. Since then, studies have also described rearrangements in NTRK2 and NTRK3. Overall, NTRK gene fusions in lung cancer occur at a frequency of ∼0.1%−1.0%. A summary of the available studies is given in the table below.
Which NTRK fusion is more frequent: NTRK1/2/3 and partners?
NTRK1/2/3 fusions occur in most cases, with NTRK1 fusions being the most frequent. No specific preference seems to exist for NTRK1/2 regarding the upstream fusion partner, whereas the most common fusion partner for NTRK3 is ETV6 (see table above).
References
- Ferlay J, Ervik M, Lam F et al. Global Cancer Observatory: Cancer Today. Lyon: International Agency for Research on Cancer; 2020 (https://gco.iarc.fr/today/fact-sheets-cancers)
- Vaishnavi A, Capelletti M, Le AT et al. Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Nat Med. 2013;19(11):1469-1472.
- Rosen EY, Goldman DA, Hechtman JF et al. TRK fusions are enriched in cancers with uncommon histologies and the absence of canonical driver mutations. Clin Cancer Res. 2020;26(7):1624-1632
- Solomon JP, Linkov I, Rosado A et al. NTRK fusion detection across multiple assays and 33,997 cases: diagnostic implications and pitfalls. Mod Pathol. 2020;33(1):38-46.
- Okamura R, Boichard A, Kato S et al. Analysis of NTRK alterations in pan-cancer adult and pediatric malignancies: implications for NTRK-targeted therapeutics. JCO Precis Oncol. 2018;2018:PO.18.00183.
- Gatalica Z, Xiu J, Swensen J, Vranic S. Molecular characterization of cancers with NTRK gene fusions. Mod Pathol. 2019;32(1):147-153.
- Farago AF, Taylor MS, Doebele RC et al. Clinicopathologic features of non-small-cell lung cancer harboring an NTRK gene fusion. JCO Precis Oncol. 2018;2018:PO.18.00037.