Fusion-mediated chromosomal instability promotes aneuploidy patterns that resemble human tumors

Cell Fusion-Mediated Tissue Regeneration as an Inducer of Polyploidy and Aneuploidy

“…Uncontrolled ploidy reduction/HST was also observed in hybrid cells derived from intrahematopoietic cell fusion events [42]. However, in contrast to these findings, other studies revealed that ploidy reduction/HST were associated with chromosome missegregation and induction of aneuploidy [7,36,39,52,54,90]. In addition to karyotypes predicted to result from a fusion between a diploid donor cell and diploid host cells (80,XXYY) or a diploid blood cell and a tetraploid hepatocyte (120,XXXXYY), many aneuploid karyotypes consisting of various combinations of autosomes and sex chromosomes were found in BMSC-derived liver cells [7].…”

“…An increased frequency of chromosomal aberrations, such as gains, losses and translocations, was also observed in highly aneuploid and tumorigenic hybrids that were derived from virus-mediated cell fusion events of normal fibroblasts with a diploid karyotype [90]. Likewise, highly aneuploid and genomic instable hybrid clones originated from fusion events between IMR90 E6-E7-HRASG12V-CFP (R-CFP) fibroblasts with IMR90 E6-E7-SmallT-hTERT-DsRed (ST-DsRed) fibroblasts [52]. Copy number variation and allele frequency analyses as well as multicolor metaphase spreads revealed a rearranged genome in hybrid cells, including gains, losses and translocation of chromosomes [52].…”

“…Likewise, highly aneuploid and genomic instable hybrid clones originated from fusion events between IMR90 E6-E7-HRASG12V-CFP (R-CFP) fibroblasts with IMR90 E6-E7-SmallT-hTERT-DsRed (ST-DsRed) fibroblasts [52]. Copy number variation and allele frequency analyses as well as multicolor metaphase spreads revealed a rearranged genome in hybrid cells, including gains, losses and translocation of chromosomes [52]. Briefly, these findings indicate that fusion of non-transformed cells can result in neoplastic hybrids.…”

“…On the one hand, aneuploidy has been associated with cancer and genomic instability, and it has even been putatively linked to the neoplastic transformation of cells [45][46][47][48]. Indeed, a few studies have already demonstrated that the fusion of nontumorigenic cells could truly give rise to tumorigenic hybrids [52][53][54]. Hence, the possibility that cancer may have its origin in an initial cell fusion event cannot be ruled out completely.…”

“…Induction of aneuploidy and genomic instability is commonly associated with cell death or senescence (for review see [47]), but data from BMSC-derived hepatocytes revealed that aneuploidy and genomic instability is tolerated in this cell type and might even be beneficial for stress-related adaptation and regeneration processes [36,39,40,[49][50][51]. In contrast, a few studies have been published indicating that cell fusion might also result in the origin of neoplastic cells due to the induction of aneuploidy and genomic instability [52][53][54].…”