Genetic evidence for tumor-hematopoietic cell hybrids in a human renal cell carcinoma metastasis

Proc Amer Assoc Cancer Res, Volume 45, 2004 1768 Previous studies using experimental animal tumor models have identified tumor-host hybrid cells through the use of heterologous genetic markers. Here we analyzed human tumor DNA for evidence of hybrid cells in a child who developed metastatic renal cell carcinoma subsequent to an allogeneic (sibling, child) bone marrow transplant. We searched for the donor’s A blood group allele within the O/O recipient’s tumor cells. Clusters of metastatic cells were laser microdissected from deparaffinized tissue sections. DNA was analyzed for restriction fragments specific for A and O alleles. Of the 21 tumor cell DNA samples tested, 16 yielded PCR products, and all 16 contained the donor A allele, while 14 of 16 also contained the O allele. The samples were isolated from diverse areas of the metastasis, and donor DNA was observed throughout. Since it was highly unlikely that renal cell carcinoma cells were transferred via the BMT, the most probable explanation is that the metastasis contained donor-recipient hybrids. Tumor cells also stained strongly for beta 1,6-branched oligosaccharides, a myeloid trait that is upregulated in experimental macrophage-tuymor fusion hybrids. The prevalence of hybrids throughout the metastasis would suggest hybridization as a potential source of metastatic cells in this patient.