In individuals with the DICER1 syndrome, most tumors arise in individuals with one inherited DICER1 mutation with an additional acquired somatic missense DICER1 mutation within the 5′ “hot-spot” codons in the RNAse IIIb domain (D1705, D1709, D1713, G1809, and E1813), ultimately activating the PI3K/AKT/mTOR pathway [15,16]. This evidence concerns the gene DICER1 and DICER1-related tumor predisposition.