A tumor landscape effect in tenosynovial giant cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells PNAS published January 6, 2006, 10.1073/pnas.0507321103 (Medical Sciences), an Open Access article.

Tenosynovial giant cell tumor (TGCT) and pigmented villonodular synovitis (PVNS) are related conditions with features of both reactive inflammatory disorders and clonal neoplastic proliferations. Chromosomal translocations involving chromosome 1q13 have previously been reported in both TGCT and PVNS. We confirm that translocations involving 1q13 are present in a majority of cases of TGCT and PVNS, and show that CSF1 is the gene at the chromosome 1q13 breakpoint. In some cases of both TGCT and PVNS, CSF1 is fused to COL6A3 (2q35). The CSF1 translocations result in overexpression of CSF1. In cases of TGCT and PVNS carrying this translocation, it is present in a minority of the intratumoral cells, leading to CSF1 expression only in these cells while the majority of cells express CSF1R but not CSF1. This suggests a tumor landscaping effect with aberrant CSF1 expression in the neoplastic cells leading to the abnormal accumulation of non-neoplastic cells that form a tumorous mass.