RESEARCH

Observations strongly suggest that cells within a tissue divide asymmetrically and are spatially entangled in their environment. Most importantly, these characteristics are always present in malignancies where the differences of chromatin in daughter cells produce a variegated gene expression in cancer.

The knowledge that cancer cell division is asymmetric and daughter cells are non-identical in terms of their chromatin (epigenetic) and gene expession affects the understanding of cancer cell behavior. Ultimately, chromatin differences directly relate to trascription where daughter cells feature between 2000 and 3000 variations in genes, which results in a highly asymmetric and heterogeneous gene expression in cancer. Therefore, the implication that asymmetry exerts on the understanding of cancer leads to significant increases in the complexity of each respective cancer being researched.

During future work, the significance of epigenetic chromatin asymmetry will continue to be explored by observing functional differences cells of the same tissue and the variability of cancer cell lines in terms of heterochromatin and the methylation of DNA.

Histone H3
The variation in methylation in transposons, which exist in massive patches, is responsible for the variation in chromatin and the methylation of histone H3. This type of variation introduces a variable in the degree of gene expression. Results from observations in cancer cell lines exhibit an extreme variation in chromatin in different daughter cells. This suggests similar variation in gene expression. Ultimately, this allows for the evolution of resistant cells and clones in cancer and cancer cell lines.

Gene Storage
Chromatin are formed at the site where DNA is methylated and the methylation will be marked by histones. If DNA is methylated, it will result in chromatin that has the spooling molecule histone H3 (lysine methylation). "Heterochromatin is characterized by the methylation of histone H3 and lysine 9 (H3Lys9), and the specific binding of heterochromatin protein 1 (HP1) to methylated H3Lys9." (Jackson, Lindroth, Cao, & Jacobsen, 2002) Observations of heterochromatin in cancer cell lines suggest a marked variation in the methylation of DNA. This is an uncontrollable variable in the use of cell lines.

Epigenetic Asymmetry:
Any molecular marker will display some degree of epigenetic asymmetry in fifty percent of the cell population. Dimorphic estrogen receptor positivity exists in invasive breast cancer. This type of feature may be present in any observable cell line or cancer. The features in this kind of dimorphic pathway suggest an asymmetric cell response and therefore an opportunity for the evolution of resistance. This also strongly suggests a differential response to therapy. In terms of single cell analysis, the results must be analyzed with the asymmetry in mind.

Methylation Blocking:
The blocking of the methylation of cytosine may be able to reduce variability that results from the high level of heterogeneity in cancer cell lines. In terms of research, epigenetic asymmetry raises the issue of cancer cell lines or cancer in tissue being much more heterogeneous than previously anticipated. The question then becomes whether this additional variability can be anticipated and minimized by blocking the degree of methylation of cytosine in any given research model. The additional level of constraint and limitation of variables may then lead to an increase in accuracy during the development of therapeutic treatment.

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