Abstract C6: Asymmetry in chromatin patterns in all cancer daughter cells
Authors: Thomas Donndelinger, Joella Skyles
Journal: Cancer Research (2011)

Abstract After the implementation of updates to the 120-year-old tissue biopsy process, newly achieved tissue detail and clarity revealed a distinct asymmetry of daughter cells and chromatin; this discovery has been observed across numerous disciplines and holds the potential to profoundly affect the research and subsequent development of treatments for every form of cancer. By using a reengineered tissue processing methodology to achieve higher levels of histological detail, the pattern of chromatin packaging was then analyzed at 1000–1600x. These phylogenetic and histological observances indicated a predominant binary feature of chromatin in daughter cells. Once identified, these differences were then interrogated with antibodies against modified histone tails. Anti-phophorylated histone H1 clearly demonstrates a distinction between chromosome sets beginning in prophase through to metaphase and telaphase. Conversely, H4 acetylated at K16 exhibit dissimilarity only in the interphase chromatin. Within these interphase cells, the nuclei of the slightly smaller daughter cells reveal more coarsely clumped chromatin both on the nuclear membrane and inside the nucleus. The cytoplasm of daughter cells also displays unique differences in reference to the degree of granulation as well as with protein expression. The same characteristics were examined in protozoans, diatoms, dictyostylium, simple metazoans, insects, and animals. This process is always present in malignancies, where the more undifferentiated tumors display greater levels of dissimilarity. With the advent of time-lapse fluorescence real-time microscopy, it becomes apparent that these variations between daughter cells are actually indicative of pairing. By altering the fundamental understanding of cancer cell biology, approaches to cancer research and treatment can then be appropriately modified. The knowledge that cancer cell division is asymmetric and daughter cells are non-identical in terms of their chromatin and gene expression affects the understanding of cancer cell behavior. In practice, cell cancer lines are poor equivalents for cancer research because cancer is dimorphic and heterogeneous in the tissue slides. Therefore, future advances in cancer treatments may stem from the awareness of both daughter phenotypes. All current concepts on cell biology, cell division, and chromatin are based on framework, understanding, and tools developed in the 19th century. After incorporating vital updates to this 120-year-old methodology, processed tissue is nearly artifact free and features deeper detail because tissue can be cut down to 0.5μm. Ultimately, these improvements allow for the observation of light and dark cells of ultra-structure under the light microscope. The foundation of these findings was established through extensive series of micrograph images and antibody-interrogated experiments, the full impact of which can only be conveyed on the poster. Given recent advances in technology and histological processing, it is now necessary to re-examine the fundamental concepts of chromatin and cellular operating systems because recognizing the existence of a cellular binary operating system has the potential to profoundly impact research in cancer biology. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C6.