Despite this, loss of function mutations in the CDKN1A gene, which encodes p21, are extremely rare in tumors (40), suggesting that p21 may not be a bona fide tumor suppressor, but rather exerts anti-tumor effects by synergizing with other tumor suppressor pathways (e.g., APC, ATM, and p53) or counteracting the activity of oncogenes, such as HRAS and Myc (26). This evidence concerns the gene APC and neoplasm.