Multiple Mechanisms by which Retroviruses Cause Tumors: Can A Virus be Ruled Out if it Doesn’t Fulfill One?

There are a number of publications suggesting that a virus highly related to mouse mammary tumor virus (MMTV) is involved in human breast cancer but this is not universally accepted. A recent paper concludes that MMTV is probably not involved in human breast cancer, based primarily on PCR data, because less than one copy of MMTV proviral DNA per cell can be found in human breast cancer samples. However, this conclusion assumes the tumor arose from a single cisactivation event due to insertional mutagenesis. Here we outline other mechanisms by which MMTV and other related retroviruses cause tumorigenesis. Since insertional mutagenesis is not the only mechanism by which retroviruses can induce tumorigenesis, we suggest that it is not yet possible to rule out a role for a virus highly related to mouse mammary tumor virus (MMTV) in human breast cancer.