Amplification of a rearranged form of the high-mobility group protein gene HMGIC in OsA-CI osteosarcoma cells.

Recently the high-mobility group protein gene HMGIC has been found to be rearranged in a variety of benign mesenchymal tumors with 12q13-q15 aberrations, such as angiomyxoma, fibroadenomas of the breast, lipomas, pleomorphic salivary gland adenomas, polyps of the endometrium, pulmonary chondroid hamartomas, and uterine leiomyomas. Here we report on HMGIC aberrations in the osteosarcoma cell line OsA-CI. In Northern blot studies, aberrant HMGIC transcripts were detected. Analysis of cDNA sequence data obtained after 3' rapid amplification of cDNA ends, indicated these to consist of 5' HMGIC sequences encoding the three DNA binding domains fused to ectopic sequences apparently derived from part of the human lumican (keratan sulphate proteoglycan) gene (LUM), which we mapped by fluorescence in situ hybridization (FISH) to chromosome 12q22-q23. Moreover, Southern blot analysis revealed amplification of this fusion gene but not of the 3'HMGIC sequences. This observation was independently confirmed by FISH analysis using yeast artificial chromosome (YAC) and cosmid clones, which furthermore indicated that the amplified 5'HMGIC sequences were contained within an amplicon of about 200 kb. Our results indicate that aberrations in HMGIC might not be restricted to benign mesenchymal tumors.