Previous findings [12–14] that mice lacking p16 or targeting DNA methylation within the p16 promoter rarely develop mammary tumors suggests that p16 loss alone is not sufficient for mammary tumorigenesis in vivo. Interestingly, loss of p16 increases MEC proliferation, rescues Brca1-deficiency induced MEC senescence, and induces mammary tumors in a Brca1-deficient background, suggesting that p16 collaborates with Brca1 to suppress mammary tumorigenesis. The gene discussed is CDKN2A; the disease is breast cancer.