The combinations of oncogenic KrasG12D with Trp53, Cdkn2a or Smad4 mutations successfully delineated the role of these genes in PC and showed that the synergistic effects of inactivating mutations of tumor suppressor genes with KrasG12D on PC progression depend on the specific inactivating mutation [8–11]. The gene discussed is CDKN2A; the disease is pachyonychia congenita.