Unlike other tumor suppressor genes such as Retinoblastoma Transcriptional Corepressor 1 (RB1) [113] or Adenomatous Polyposis Coli (APC) [114], which follow the Knudson’s “two hit” hypothesis for their inactivation [115], PTEN function was demonstrated to be impaired by even a modest reduction of its expression levels, thus behaving as a cancer susceptibility gene [116]. This evidence concerns the gene PTEN and neoplasm.