Among these, 8 tumor-suppressor genes are worth mentioning (EP300, CREBBP, CTNND1, SMAD3, SMARCA4, SPEN, TNFAIP3, and TSC2), as well as genes that control normal cell proliferation and differentiation, such as IGF1R, JUN, and ERBB3, to suggest the interesting possibility that the PIWIL1–piRNA machinery may participate in tumorigenesis by directly regulating the activity of these genes. Here, SMAD3 is linked to neoplasm.