Interestingly, ablation of Pten and Trp53 along with Rb1 [56,57] or Rb-family members [34] gives rise to high grade neuroendocrine tumors, supporting the role of pRb in neuroendocrine differentiation in a context of Pten and Trp53 loss. This evidence concerns the gene TP53 and neuroendocrine neoplasm.