Current strategies to determine tumor * normal (TN)-hybrid cells among human cancer\ncells include the detection of hematopoietic markers and other mesodermal markers on tumor cells or\nthe presence of donor DNA in cancer samples from patients who had previously received an allogenic\nbone marrow transplant. By doing so, several studies have demonstrated that TN-hybrid cells could\nbe found in human cancers. However, a prerequisite of this cell fusion search strategy is that such\nmarkers are stably expressed by TN-hybrid cells over time. However, cell fusion is a potent inducer\nof genomic instability, and TN-hybrid cells may lose these cell fusion markers, thereby becoming\nindistinguishable from nonfused tumor cells. In addition, hybrid cells can evolve from homotypic\nfusion events between tumor cells or from heterotypic fusion events between tumor cells and normal\ncells possessing similar markers, which would also be indistinguishable from nonfused tumor cells.\nSuch indistinguishable or invisible hybrid cells will be referred to as dark matter hybrids, which\ncannot as yet be detected and quantified, but which contribute to tumor growth and progression.
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