A stem cell fusion model of carcinogenesis.

The origin of cancer remains enigmatic. Current models of carcinogenesis based on the gene mutation hypothesis have limitations in explaining many aspects of cancer. We put forward a new model of multistage carcinogenesis and propose that cancer development involves gene mutations and cell fusions. Specifically, cancer can result from a fusion between an "altered" pre-malignant cell and a bone marrow-derived stem cell (BMDSC). "Aneuploidy", which is a hallmark of malignancy, is a direct consequence of this cell fusion. The "stem cell fusion" model explains the remarkable similarities between malignant cells and BMDSC. This model also explains why non-mutagens can be carcinogens, and why non-mutagenic processes, such as wound healing and chronic inflammation, can promote malignant transformation. This model is readily testable. Cancer has been difficult to treat because of tissue heterogeneity and gene instability. However, if the malignant characteristics of cancer cells are derived from BMDSC, new conserved targets such as homing receptors for designing novel therapies may emerge.