Infantile fibrosarcoma and congenital mesoblastic nephroma are tumors of infancy traditionally associated with the ETV6-NTRK3 gene fusion. However, a number of case reports have identified variant fusions in these tumors. In order to assess the frequency of variant NTRK3 fusions, and in particular whether the recently identified EML4-NTRK3 fusion is recurrent, 63 archival cases of infantile fibrosarcoma, congenital mesoblastic nephroma, mammary analog secretory carcinoma and secretory breast carcinoma (tumor types that are known to carry recurrent ETV6-NTRK3 fusions) were tested with NTRK3 break-apart FISH, EML4-NTRK3 dual fusion FISH, and targeted RNA sequencing. The EML4-NTRK3 fusion was identified in two cases of infantile fibrosarcoma (one of which was previously described), and in one case of congenital mesoblastic nephroma, demonstrating that the EML4-NTRK3 fusion is a recurrent genetic event in these related tumors. The growing spectrum of gene fusions associated with infantile fibrosarcoma and congenital mesoblastic nephroma along with the recent availability of targeted therapies directed toward inhibition of NTRK signaling argue for alternate testing strategies beyond ETV6 break-apart FISH. The use of either NTRK3 FISH or next-generation sequencing will expand the number of cases in which an oncogenic fusion is identified and facilitate optimal diagnosis and treatment for patients.

• MeSH
• Adult MeSH
• Fibrosarcoma diagnosis   genetics   MeSH
• Oncogene Proteins, Fusion genetics   MeSH
• Genetic Testing MeSH
• In Situ Hybridization, Fluorescence MeSH
• Carcinoma genetics   MeSH
• Infant MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local genetics   MeSH
• Nephroma, Mesoblastic congenital   diagnosis   genetics   MeSH
• Adolescent MeSH
• Kidney Neoplasms congenital   diagnosis   genetics   MeSH
• Breast Neoplasms genetics   MeSH
• Infant, Newborn MeSH
• Child, Preschool MeSH
• Microtubule-Associated Proteins genetics   MeSH
• Cell Cycle Proteins genetics   MeSH
• Proto-Oncogene Proteins c-ets genetics   MeSH
• Discoidin Domain Receptor 2 genetics   MeSH
• Repressor Proteins genetics   MeSH
• Sequence Analysis, RNA MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Serine Endopeptidases genetics   MeSH
• Check Tag
• Adult MeSH
• Infant MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Infant, Newborn MeSH
• Child, Preschool MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Afatinib MeSH
• Gene Amplification MeSH
• Carcinoma, Basosquamous MeSH
• Quinazolines * administration & dosage   pharmacokinetics   adverse effects   therapeutic use   MeSH
• Adult MeSH
• Erlotinib Hydrochloride * administration & dosage   pharmacokinetics   adverse effects   therapeutic use   MeSH
• Genes, erbB-2 MeSH
• Drug Evaluation MeSH
• Clinical Trials, Phase III as Topic MeSH
• Humans MeSH
• Multicenter Studies as Topic MeSH
• Mutation MeSH
• Lung Neoplasms * drug therapy   MeSH
• Carcinoma, Non-Small-Cell Lung * drug therapy   MeSH
• Disease Progression MeSH
• Randomized Controlled Trials as Topic MeSH
• Discoidin Domain Receptor 2 MeSH
• Receptor, Fibroblast Growth Factor, Type 1 MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Publication type
• Clinical Study MeSH