ETV6NTRK3positive

ETV6NTRK3positive refers to cells, tumors, or specimens that carry the ETV6-NTRK3 gene fusion, created by a chromosomal translocation t(12;15)(p13;q25). The fusion creates a constitutively active tyrosine kinase that drives oncogenic signaling, principally through the MAPK/ERK and PI3K/AKT pathways, promoting proliferation and survival of neoplastic cells. The fusion is a characteristic molecular hallmark of several pediatric and adult tumors.

Clinically, ETV6-NTRK3 fusion is most closely associated with infantile fibrosarcoma, a soft tissue sarcoma typically occurring in infancy, where it is considered diagnostic. It is also found in mammary analogue secretory carcinoma of the breast, previously termed secretory carcinoma, and in a subset of other TRK fusion–positive tumors. The presence of the fusion can aid in diagnosis and classification and may have prognostic implications depending on tumor type.

Detection methods include reverse transcription PCR and fluorescence in situ hybridization to identify the ETV6-NTRK3 fusion transcript or gene rearrangement, and next-generation sequencing approaches that can detect fusion breakpoints. Immunohistochemistry for pan-TRK proteins can provide a screening signal but is not definitive for ETV6-NTRK3 specifically.

Therapeutic implications are significant: tumors harboring NTRK fusions, including ETV6-NTRK3, may respond to TRK inhibitors such as larotrectinib and entrectinib, across tumor types. However, resistance can develop through additional mutations in the NTRK kinase domain or alternative signaling changes. Ongoing research seeks to refine diagnostic algorithms and optimize targeted therapy in ETV6-NTRK3 positive neoplasms.