A NOVEL ETV6-NTRK3 GENE FUSION IN CONGENITAL FIBROSARCOMA

Congenital (or infantile) fibrosarcoma (CFS) is a malignant tumour of fibroblasts that occurs in patients aged two years or younger. CFS is unique among human sarcomas in that it has an excellent prognosis and very low metastatic rate(1,2). CFS is histologically identical to adul t-type fibrosarcoma (ATFS); however, ATFS is an aggressive malignancy of adults and older children that has a poor prognosis(3). We report a novel recurrent t(12;15)(p13;q25) rearrangement in CFS that may under lie the distinctive biological properties of this tumour. By cloning t he chromosome breakpoints, we show that the rearrangement fuses the ET V6 (also known as TEL) gene from 12p13 with the 15q25 NTRK3 neurotroph in-3 receptor gene (also known as TRKC). Analysis of mRNA revealed the expression of ETV6-NTRK3 chimaeric transcripts in all three CFS tumou rs analysed. These were not detected in ATFS or infantile fibromatosis (IFB), a histologically similar but benign fibroblastic proliferation occurring in the same age-group as CFS. ETV6-NTRK3 fusion transcripts encode the helix-loop-helix (HLH) protein dimerization domain of ETV6 fused to the protein tyrosine kinase (PTK) domain of NTRK3. Our studi es indicate that a chimaeric PTK is expressed in CFS and this may cont ribute to oncogenesis by dysregulation of NTRK3 signal transduction pa thways. Moreover, ETV6-NTRK3 gene fusions provide a potential diagnost ic marker for CFS.