The CDKN2A (INK4a/ARF) locus encodes two distinct cell cycle inhibitors, p16^Ink4a and p19^ARF, both of which have been implicated in tumorigenesis. In the September 6 Nature, two independent groups report the generation of knockout mice specifically lacking p16^Ink4a. Surprisingly, mouse embryonic fibroblasts (MEFs) lacking p16^Ink4a were normal in terms of growth characteristics, senescence phenotypes and resistance to oncogenic Ras-induced transformation.

These observations are in contrast to results obtained with p19^ARF-null fibroblasts. But both groups provide evidence for a role in tumour suppression: Krimpenfort et al. report that p16Ink4a mutation results in a susceptibility to spontaneous and carcinogen-induced melanoma formation (Nature 2001, 413:83-86). Sharpless et al. also found sarcomas, adenomas and lymphomas (Nature 2001, 413:86-91). These results establish that the CDKN2A locus does indeed contain two distinct tumour suppressor genes.