**4. The cancer as an epigenetic process**

The process of cancer development involves genomic changes identified as genetic and also changes in the epigenetic information (Jones & Baylin, 2002; Hake et al., 2004; McGarvey et al., 2008). Altered DNA methylation patterns have been described and histone modifications in cancer cells may occur at different stages of tumor development and contribute to the development and progression of cancer (Galm et al., 2006; McGarvey et al., 2008).

Historically, the first evidence has emerged that the contribution of epigenetics to cancer development comes from nuclear transfer experiments. Nuclear transfer provides a tool for selective reprogramming of the epigenetic state of a cell genome, without changing their genetic constitution, with the purpose of assessing the role of epigenetics in tumorigenesis.

Experiments with frogs have shown that renal carcinoma nuclei can be reprogrammed to support embryonic development at the tadpole stage (McKinnell et al. 1969). Similar results were also obtained with nuclei from medulloblastoma in mice (Li et al. 2003). Therefore, the nuclei of cancer cells can be reprogrammed through a process of nuclear transfer.

Another experimental approach was also based on nuclear transfer with blastocyst formation. However, it included the creation of explants from the inner cell mass in "in vitro" culture to develop embryonic stem cell lines (Hochedlinger et al., 2004). These

Epigenetics is the study of heritable changes in phenotype or gene expression caused by mechanisms other than changes in DNA sequence. The molecular mechanisms of epigenetic inheritance and its relationship with the expression of chromatin include three interrelated processes, namely DNA methylation, genomic imprinting and histone modifications (Kouzarides, 2007). Through small chemical molecules called methyl groups, which bind covalently with DNA or histones, the epigenetic processes improve the ability of genome to store and transmit biological information beyond the known structure and sequence of

In recent years we have faced a new paradigm, a view more focused on the cell and on the search for information layers outside of the cell nucleus and even of the DNA as the center for information of the cell. These layers of epigenetic information transcend embryogenesis

The importance of epigenetics in experimental biology is decisively felt in the process of cell differentiation. The information and epigenetic marks are essential to determine which cell is phenotypically different from any other cell as a result of embryogenesis. This allows us to reprogram a somatic cell and transform it based on epigenetic principles, in a cell with characteristics of pluripotent stem cells. These cells are called ips cells (induced pluripotent stem cells)(Takahashi et al., 2007). In the Ips cells the DNA has not been changed or modified and the pluripotent state can be inherited during each cell division. This indicates that the changes in the machinery of epigenetic information, rather than genetic material,

The process of cancer development involves genomic changes identified as genetic and also changes in the epigenetic information (Jones & Baylin, 2002; Hake et al., 2004; McGarvey et al., 2008). Altered DNA methylation patterns have been described and histone modifications in cancer cells may occur at different stages of tumor development and contribute to the

Historically, the first evidence has emerged that the contribution of epigenetics to cancer development comes from nuclear transfer experiments. Nuclear transfer provides a tool for selective reprogramming of the epigenetic state of a cell genome, without changing their genetic constitution, with the purpose of assessing the role of epigenetics in tumorigenesis. Experiments with frogs have shown that renal carcinoma nuclei can be reprogrammed to support embryonic development at the tadpole stage (McKinnell et al. 1969). Similar results were also obtained with nuclei from medulloblastoma in mice (Li et al. 2003). Therefore, the

Another experimental approach was also based on nuclear transfer with blastocyst formation. However, it included the creation of explants from the inner cell mass in "in vitro" culture to develop embryonic stem cell lines (Hochedlinger et al., 2004). These

development and progression of cancer (Galm et al., 2006; McGarvey et al., 2008).

nuclei of cancer cells can be reprogrammed through a process of nuclear transfer.

**2. Epigenetics** 

genetic material.

and cancer development processes, as follows.

play a decisive role in controlling differentiation.

**4. The cancer as an epigenetic process** 

**3. The embryogenesis as an epigenetic process** 

embryonic stem cells were used to confirm the origin of the tumor clone and test the initial conservation of the tumorigenic capacity of these cells originated by tumor cores. In these experiments it has been unequivocally demonstrated that the clones derived from cancer cells and that the nuclei of cancer cells (leukemia, lymphoma and breast cancer) were able to sustain the embryonic development until the preimplantation blastocyst stage. It has also been demonstrated that the oocyte cytoplasm is able to reprogram the epigenetic state of some nuclei of tumor cells, transforming these cells into pluripotent and also enabling them to sustain the differentiation of multiple somatic cell types such as melanocytes, lymphocytes and fibloblasts. Therefore, the cancer state is an epigenetic cell state susceptible of change regardless of the DNA alterations (Feinberg, 2008).

The role of epigenetics was also confirmed by studying cohorts of twins and analyzing the concordance in cancer between monozygotic and dizygotic twins, and, thus, providing information about whether family patterns are influenced by environmental or genetic patterns. If the concordance in cancer is greater between monozygotic twins (who share 100% of the genes) than between dizygotic twins (who share in average 50% of the segregated genes) the genetic effects are probably more important. On the other hand, if the concordance rate is similar in both types of twins, then the environmental effects are probably more important. Thus, the use of statistics to analyze large populations of twins allows us to estimate the magnitude of environmental and genetic effects on susceptibility to sporadic cancer.

This retrospective study has shown that hereditary factors make a minor contribution to susceptibility to most types of neoplasms, indicating that the environment plays a major role in sporadic cancer in populations living in the study areas (Lichtenstein et al., 2000). The study, on the other hand, stresses that some types of cancer, such as prostate and colorectal cancers are more influenced by genetic factors than previously thought.

Thus, even more important aspects related to diseases are being reworked, and cancer may no longer be categorized as a disease based on genetics alone, and all the data indicate that most commonly diagnosed cancers in the world have primarily environmental or epigenetic origin. Except for some types of cancer considered hereditary, familial adenomatous polyposis, colorectal cancer and prostate cancer, the contribution of hereditary factors to the development of cancer is thought to be relatively small.
