Since numerous tumors have been shown to originate from tissue stem cells (Visvader, 2011), it has been proposed that CACs are the cell of origin for PanINs and PDA (Miyamoto et al., 2003; Stanger et al., 2005). However, this contention has not been directly tested, largely because genetic tools to target ductal and CACs have only recently been generated (Kopp et al., 2011; Solar et al., 2009).

Interestingly, these tumors did not manifest mutations in any of the other TSG pathways noted above. This raises the question of whether other TSG mutations alter the biology of the disease. For example, additional mutations may be required to develop a significant metastatic burden.