Spontaneous additional mutations have been demonstrated to accumulate along with epigenetic events resulting in an increased level of genetic complexity in human cancer.36 The mouse model reported here is unique in that it harbors a PI3KCA (p110α) oncogene, which is frequently mutated in many human cancers,3, 6 along with the tumor suppressor gene p53 deletion and a well-known oncogene, KrasG12D. Here, TP53 is linked to cancer.