Molecular identification of COL6A3-CSF1 fusion transcripts in tenosynovial giant cell tumors

Tenosynovial giant cell tumors (TGCTs) are benign lesions of the tendon sheaths that primarily affect the fingers, ankles, or feet. Cytogenetic data have shown that 1p13 is most frequently involved in structural aberrations and that 2q37 is its most common translocation partner. The genes involved in the translocation t(1;2)(p13;q37) were recently identified: the colony-stimulating factor-1 (CSF1 or M-CSF1) at 1p13 and the collagen type VI alpha-3 (COL6A3) at 2q37. Based upon the suggestion that a fusion of these genes through the translocation would result in overexpression of CSF1 due to a strong COL6A3 promoter, we performed RT-PCR on six TGCT cases with t(1;2) to search for a putative COL6A3-CSF1 fusion gene. Such fusion transcripts were detected in three cases of which one was an in-frame fusion. In all cases, however, the breakpoints in CSF1 appeared downstream of exon 5, indicating that the amino-terminal part of CSF1, which interacts with its receptor CSF1R, is not encoded by the the chimeric transcripts we identified. The pathogenetic mechanism of these chimeric transcripts is therefore unclear