Among the orthologous genes obtained from intersecting the mouse and human LaD gene sets, two genes have previously been reported with roles in embryogenesis. Kcnq1 was reported to be a paternally imprinted gene that is down regulated during embryogenesis development. The Cyclic GMP-Inhibited Phosphodiesterase 3A gene functions in the cGMP-PKG signaling pathway. PDE3A must be inhibited to allow expression of other important genes during physiological development. Hence, under the global hypomethylation state during BAY 73-4506 VEGFR/PDGFR inhibitor zygotic activity, intragenic L1 may be expressed which down-regulates these genes, perhaps by the same AGO2-dependent mechanism as described in cancer cells. Although these tests are suggestive for possible function of intragenic L1s in mouse and human such as X-inactivation and embryogenesis, there are alternative explanations that do not require L1s to have functions. For example, some rodent species thought to lack potentially mobile L1 still have X-inactivation. In addition, accumulation of L1 elements in X still continues even when X-inactivation is not needed in Tokudaia osimensis, an XO species. The reason for conservation of intragenic L1s could stem from the genomic context that these elements are located, i.e., genic regions are likely to be more constrained by background selection, hence conservation of intragenic L1s does not necessarily imply function. Therefore, apart from direct testing for function, e.g., L1 ablation by genome editing tool, comparison among a greater range of mammalian species could provide insights into putative functions of conserved L1s. This is because a recent intragenic L1 element is unlikely to have a function and is tolerated because it has minor phenotypic consequence. On the other hand, if an intragenic L1 element has persisted for a long evolutionary time, it may have acquired a new function which can be constrained by purifying selection. The development of cancer is a multistep process that is believed to result from accumulation of genetic alterations in a single cell during the life of an individual. The number of genes found to be associated with different cancers is growing rapidly. The most frequently activated genes are members of the RAS gene family, two of which and were first identified as being homologous to viral transforming genes, while the third was identified in a human neuroblastoma. The RAS gene product is a monomeric membrane-localized G protein of 21 kd that functions as a molecular switch linking receptor and non-receptor tyrosine kinase activation to downstream cytoplasmic or nuclear events. Each mammalian cell contains at least three distinct RAS protooncogenes encoding closely related, but distinct proteins. RAS genes can be activated by various point mutations including those affecting codons 12, 13, 61, or 113–117. Signal transduction by ras proteins involves hydrolysis of GTP, and activating mutations inhibit this process, locking the protein in the “on” signaling conformation. Activating mutations in these RAS proteins result in constitutive signaling, thereby stimulating cell proliferation, and inhibiting apoptosis.