Epidemiology of Cancers With NTRK Gene Fusion

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NTRK gene fusions are found across several adult and paediatric tumour types and across diverse tissue and cell lineages. NTRK gene fusions can be grouped according to the frequency at which they are detected [1-6]:

1. Rare cancers, which are enriched for NTRK gene fusion (detected at a prevalence of >90%) to the extent that these alterations can be considered diagnostic features of the tumour (e.g. as for mammary analogue secretory carcinoma [MASC] and secretory carcinoma of the breast). These are also known as high-prevalence tumours.
2. More common cancers (e.g. lung cancer), in which NTRK gene fusion are rare (i.e. mostly detected at a prevalence of 5-25% or <5%, also known as low-prevalence tumours).

NTRK fusions have been reported to have similar prevalence in both adult and paediatric tumours; approximately 0.3% across all tumour types. The most common partners are NTRK1 and NTRK3 and the most frequent fusion is ETV6-NTRK3.

The prevalence of NTRK gene fusions in various tumor types

*Approximate % and ranking based on data from [1-6].

These observations have been confirmed recently using genomic profiling data analyzed from the FoundationCORE® real-world database. Out of >295,000 cancer patients NTRK gene fusions were found in 889, a prevalence of 0.30% among 45 different tumour types. NTRK gene fusion prevalence varied greatly by age, cancer type and histology. Across all cases, prevalence was 0.28% and 1.34% in patients aged ≥18 and <18 years, respectively and was highest in patients <5 years (2.28%). In terms of tumour types, the highest prevalence of NTRK fusions was observed in salivary gland tumours (2.62%) [7].

The rarity of these genomic abnormalities and their scattered incidence across tumour types have made it challenging to detect TRK fusion proteins.  However, there are several approaches to test for NTRK gene fusion that are available. You can learn more about testing for NTRK gene fusion in Module 2.

Frequency And Sites of NTRK Gene Fusions in Adult and Paediatric Cancers [1]

^aFound in adult cancers only, unless indicated; ^bFound in adult and paediatric cases; ^cFound in adult cases as thyroid cancer and papillary thyroid cancer in paediatric cases; ^dFound in paediatric cases only.

MASC, mammary analogue secretory carcinoma.

Frequency And Types of NTRK gene fusion in Adult and Paediatric Cancers^a [2]

§ Overview generated based on data reported in [2-6]

ALL, acute lymphoblastic leukaemia, GIST, gastrointestinal stromal tumours; MASC, mammary analogue secretory carcinoma.

References

1. Cocco E, Scaltriti M, Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol 2018; 15: 731-747.
2. Chen Y, Chi P. Basket trial of TRK inhibitors demonstrates efficacy in TRK fusion-positive cancers. J Hematol Oncol 2018; 11: 78.
3. Gatalica Z, Xiu J, Swensen J, Vranic S. Molecular characterization of cancers with NTRK gene fusions. Mod Pathol. 2019;32(1):147–153.
4. 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.

5. Conde E, Hernandez S, Sanchez E, Regojo RM, Camacho C, Alonso M, Martinez R, Lopez-Rios F. Pan-TRK Immunohistochemistry: An Example-Based Practical Approach to Efficiently Identify Patients With NTRK Fusion Cancer. Arch Pathol Lab Med. 2021; 145(8):1031-1040.

6. Solomon JP, Linkov I, Rosado A, Mullaney K, Rosen EY, Frosina D, Jungbluth AA, Zehir A, Benayed R, Drilon A, Hyman DM, Ladanyi M, Sireci AN, Hechtman JF. NTRK fusion detection across multiple assays and 33,997 cases: diagnostic implications and pitfalls. Mod Pathol. 2020; 33(1):38-46.

7. Westphalen CB, Krebs MG, Le Tourneau C, Sokol ES, Maund SL, Wilson TR, Jin DX, Newberg JY, Fabrizio D, Veronese L, Thomas M, de Braud F. Genomic context of NTRK1/2/3 fusion-positive tumours from a large real-world population. NPJ Precis Oncol. 2021 Jul 20;5(1):69.