The oncogerminative CSC is the only cell of the heterogeneous tumor-cell population that is able to metastasize and develop into a metastatic tumor. achieves immortality by passing through the stages of its life-cycle and developing into a pseudo-blastula-stage embryo, which manifests in the body as a malignant tumor. In this view, the development of a malignant tumor from a CSC is usually a phenomenon of developmental biology, which we named a desperate asexual self-cloning event. The theory explains seven core characteristics of malignant tumors: (1) CSC immortality, (2) multistep development of a malignant tumor from a single CSC, (3) heterogeneity of malignant tumor cell populations, (4) metastatic spread of CSCs, (5) invasive growth, (6) malignant progression, and (7) selective immune tolerance toward malignancy cells. The Oncogerminative Theory of Tumorigenesis suggests new avenues for discovery of revolutionary therapies to treat, prevent, and eradicate malignancy. lethal3 malignant brain tumors (L(3)mbt) exhibit a soma-to-germline transformation through the ectopic expression of genes normally required for germline stemness, Istradefylline (KW-6002) fitness, or longevity. Inactivation of any of the germline genes (nanos, vasa, piwi, or aubergine) suppressed the malignant growth of L(3)mbt. Marilyn Monk and Cathy Holding29 hypothesized that human pre-implantation embryonic cells Mela are comparable in phenotype to malignancy cells. Both types of cell undergo reprogramming to a proliferative Istradefylline (KW-6002) stem cell state and become potentially immortal and invasive. To test the hypothesis that embryonic genes are re-expressed in malignancy cells, the authors prepare amplified cDNA from human individual preimplantation embryos and isolate embryo-specific sequences. Then these Istradefylline (KW-6002) isolated embryo-specific genes were tested for their expression in a panel of human cancers. It was found that three of the five embryo-expressed cDNA sequences tested were re-expressed in cells of different tumors. The authors also tested a range of malignancy cell lines for expression of embryo and/or malignancy genes C and E and of OCT4. All three gene sequences were expressed in various malignancy cell lines but not in immortalized fibroblasts.29 Therefore, it might be expected that cancer cells will express genes that are expressed in very early embryonic cells, especially genes specifically associated with reprogramming, and will return to the undifferentiated and proliferative stem cell state that is associated with immortality and invasiveness. Genes that are specific to this unique early phase of the human life cycle and that are not expressed in committed somatic cells and immortalized normal cells (fibroblasts) may have greater potential for being targeted in malignancy treatment. A similar genetic event occurs in the early embryo during establishment of its germ cell lineage. As is well known, the pluripotent epiblast cells in the early embryo are destined to form both somatic cells and primordial germ cells. In the few cells that undergo specification to establish the germ cell lineage, there is a repression of the somatic program. So, the general characteristic of germ cell specification is that the expression of somatic genes must be repressed for the germ cell program to eventually be initiated.30 Akira Nakamura and colleagues explained the cell biology of germ cell formation, along with how the germplasm prospects to the repression of somatic gene expression (for a review observe ref. 31). Recent evidence shows that Blimp1, a known transcriptional repressor with a SET/PR domain, is crucial for the specification of primordial germ cells (PGCs). Blimp1 (Prdm1), the key determinant of PGCs, plays a combinatorial role with Prdm14 during PGC specification from postimplantation epiblast cells. They together initiate epigenetic reprogramming in early germ cells toward an underlying pluripotent state, which is equivalent to the state of embryonic stem cells (ESCs).32,33 Blimp1 has the role, at least in part, of suppressing the cells somatic program.34 Jekaterina Erenpreisa and Mark S Cragg observed the activation of meiotic genes in cancer cells during reversible polyploidy induced by DNA damage.25,26 The upregulation of key meiotic genes (MOS, REC8, SGO1, SGO2, DMC1, SPO11, SCYP1,2,3, STAG3) was found, and was associated with reversible polyploidy in TP53-deficient lymphoma, breast, colon, ovarian, and cervical cancer cell lines after irradiation or spindle damage (for a review see refs. 35C38). The ectopic expression of important meiotic genes such as was also found in main non-small cell lung carcinoma,.