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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, 2]:

  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).

The rarity of these genomic abnormalities and their scattered incidence across various tumour types has 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.

Figure 5: Frequency And Sites of NTRK Gene Fusions in Adult and Paediatric Cancers [1]

Figure 5: Frequency And Sites of NTRK Gene Fusions in Adult and Paediatric Cancers

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.

Figure 6: Frequency And Types of NTRK gene fusion in Adult and Paediatric Cancers[2]

Figure 6: Frequency And Types of NTRK gene fusion in Adult and Paediatric Cancers

aAs reported by Chen and Chi. 2018.
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.

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