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Using comparative genomic hybridization (CGH), we have identified and mapped regions of DNA amplification in primary and metastatic osteosarcomas. Samples were obtained from four patients and ten independent xenografts. Sixty‐four percent of the tumors showed increased DNA‐sequence copy numbers, affecting 23 different chromosomal sites. Most of these regions were not previously associated with the development and/or progression of these tumors. Amplicons originating from 1q21–q23, 6p, 8q23‐qter, and 17p11‐p12 were observed most frequently. The 6p and 17p11–p12 amplicons seem to be specific for osteosarcomas, indicating that these regions may harbor genes relevant for the development of these tumors.

Comparative genomic hybridization (C GH

Abstract. The E48 antigen, a putative human homologue of the 20-kD protein present in desmosomal preparations of bovine muzzle, and formerly called desmoglein III (dg4), is a promising target antigen for antibody-based therapy of squamous cell carcinoma in man. To anticipate the effect of high antibody dose treatment, and to evaluate the possible biological involvement of the antigen in carcinogenesis, we set out to molecularly characterize the antigen. A cDNA clone encoding the E48 antigen was isolated by expression cloning in COS cells. Sequence analysis revealed that the clone contained an open reading frame of 128 amino acids, encoding a core protein of 13,286 kD. Database searching showed that the E48 antigen has a high level of sequence similarity with the mouse ThB antigen, a member of the Ly-6 antigen family. Phosphatidylinositol-specific (PI-specific) phospholipase-C treatment indicated that the E48 antigen is glycosylphosphatidylinositol-anchored (GPI-anchored) to the plasma membrane. The gene encoding the E48 antigen is a single copy gene, located on human chromosome 8 in the 8q24-qter region. The expression of the gene is confined to keratinocytes and squamous tumor cells. The putative mouse homologue, the ThB antigen, originally identified as an antigen on cells of the lymphocyte lineage, was shown to be highly expressed in squamous mouse epithelia. Moreover, the ThB expression level is in keratinocytes, in contrast to that in lymphocytes, not mouse strain related. Transfection of mouse SV40-polyoma transformed mouse NIH/3T3 cells with the E48 cDNA confirmed that the antigen is likely to be involved in cell-cell adhesion.

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