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
• dospělí MeSH
• fibrosarkom diagnóza   genetika   MeSH
• fúzní onkogenní proteiny genetika   MeSH
• genetické testování MeSH
• hybridizace in situ fluorescenční MeSH
• karcinom genetika   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru genetika   MeSH
• mezoblastický nefrom vrozené   diagnóza   genetika   MeSH
• mladiství MeSH
• nádory ledvin vrozené   diagnóza   genetika   MeSH
• nádory prsu genetika   MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• proteiny asociované s mikrotubuly genetika   MeSH
• proteiny buněčného cyklu genetika   MeSH
• protoonkogenní proteiny c-ets genetika   MeSH
• receptor DDR2 genetika   MeSH
• represorové proteiny genetika   MeSH
• sekvenční analýza RNA MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• serinové endopeptidasy genetika   MeSH
• Check Tag
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

We describe a novel gene fusion, EWSR1-CREM, identified in 3 cases of clear cell carcinoma (CCC) using anchored multiplex polymerase chain reaction, a next-generation sequencing-based technique. CCC is a low-grade salivary tumor recently characterized to have EWSR1-ATF1 fusions in the majority of cases. Three cases of malignant tumor presenting in the base of tongue, lung, and nasopharynx were studied. All cases shared a clear cell morphology with hyalinized stroma, presence of mucin and p63 positivity and were initially diagnosed as mucoepidermoid carcinoma but were negative for evidence of any of the expected gene fusions. Anchored multiplex polymerase chain reaction demonstrated a EWSR1-CREM fusion in all 3 cases to confirm a diagnosis of CCC. This finding is biologically justified as CREM and ATF1 both belong to the CREB family of transcription factors. EWSR1-CREM fusions have not been previously reported in CCC and have only rarely been reported in other tumors. We show that the ability to discover novel gene variants with next-generation sequencing-based assays has clinical utility in the pathologic classification of fusion gene-associated tumors.

• MeSH
• adenokarcinom z jasných buněk genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• modulátor elementu responzivního pro cyklický AMP genetika   MeSH
• nádory jazyka genetika   patologie   MeSH
• nádory nosohltanu genetika   MeSH
• nádory plic genetika   patologie   MeSH
• onkogenní fúze MeSH
• protein EWS vázající RNA genetika   MeSH
• senioři MeSH
• stanovení celkové genové exprese MeSH
• transkriptom MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH