GLI1 amplification and fusion in MDM2-amplified low-grade osteosarcoma

Glioma-associated oncogene homologue 1 (GLI1) was recently shown to be coamplified with mouse double minute 2 (MDM2), cyclin-dependent kinase 4 (CDK4) and some other adjacent genes in a significant subset of GLI1-altered mesenchymal tumours and well-differentiated/dedifferentiated liposarcomas, which are characterised by MDM2 amplification. Given that MDM2 is also amplified in low-grade osteosarcoma (LGOS), we investigated the prevalence of GLI1 amplifications/fusions in a series of 15 cases of MDM2-amplified LGOS, an area that has not been previously explored.

This study conducted a retrospective analysis and examined GLI1 amplifications/fusions in 15 cases of MDM2-amplified LGOS and 46 cases of other bone tumours and tumour-like lesions using fluorescence in situ hybridisation with a GLI1 amplification probe and a GLI1 break-apart probe. Six cases of LGOS were also tested by next-generation sequencing.

Fluorescence in situ hybridisation analysis revealed that 13 of 15 (87%) LGOS cases exhibited GLI1 amplification; no fusion gene was found. Next-generation sequencing revealed that all six tested cases showed GLI1 amplification and one case had both GLI1 amplification and GLI1 gene fusion (PPM1H::GLI1). All 46 cases of other bone tumours and tumour-like lesions were negative for GLI1 amplification and GLI1 fusion.

These results indicate that GLI1 amplification is common in LGOS, and GLI1 fusion could occur in LGOS.