Genome reversion process of endopolyploidy confers chromosome instability on the descendent diploid cells

Abstract

Endotetraploidy with 4-chromatid chromosomes divides by a bipolar, 2-step meiotic-like division back to diploidy (subcells), which is chiefly achieved by co-segregation of whole genomes uncoupled from spindle participation. This study shows diploid subcell inheritance of endopolyploid-division traits: perpendicular division relative to the cytoskeleton axis, dysfunctional centromere/kinetochore regions and whole genomic separations from co-segregation. The assimilation of these traits into the innate mitotic machinery of the subcells resulted in diploid mitotic divisions that tolerated mild disturbances in cycling progression and in chromosomal distributions. The data were interpreted as demonstrating a blending together of endopolyploid and mitotic division traits with result of an endo-modified mitosis in subcell propagation. Additionally, chromosomal stickiness caused breakage in anaphase/telophase. The observations are discussed in regard to a potential for slowly developing aneuploidy with increasing genomic complexity, which is widely accepted to be the basic route in tumorigenesis.

Cancers in Children Ages 8 to 12 Are Injury-Related

“…Sick cells with genomic (DNA) damage must for survival-associated propagative ability repair the damage. Such cells from natural (dysfunctional telomeres) and induced sources (chemical, X-ray) showed changes to endo-tetraploidization (not regular doubling to 92 chromosomes) that could undergo a transient, mechanistic, genome reductive division (meiotic-like) to genome, altered progeny cells [2]- [5]. Inn passage-growth these altered cells expressed neoplastic-like phenotypes, including gain of a proliferative advantage (GPA) [3].…”

Normal Human Cells Acquiring Proliferative Advantage to Hyperplasia-Like Growth-Morphology: Aberrant Progeny Cells Associated With Endopolyploid and Haploid Divisions

“…The question is therefore, whether there are known abnormal cellular events that can originate in normal cells and, lead to aneuploidy and CIN-cells? The answer is yes, the mechanism of endopolyploid genome reductive divisions (Wolfe, 2001) produce genome unstable, diploid progeny cells (Walen, 2006(Walen, , 2007a2010;2012;Lee et al, 2009;Erenpreisa et al, 2011).…”

Neoplastic-Like CELL Changes of Normal Fibroblast Cells Associated with Evolutionary Conserved Maternal and Paternal Genomic Autonomous Behavior (Gonomery)

“…These divisions are orderly to daughter cells, which have inherited endo-division special traits as for instance co-segregation of complete complements. Such traits became incorporated into the daughter' innate mitotic machinery best expressed by prophase cell' ability to segregate complete genomes directly into anaphase [12]. If for example, the acknowledged presence of tetraploid diplochromosomal cells had been considered with division-results, the claim of a "transformed cell phenotype" from presence of trisomy 8 sole-abnormality would be radically different [34].…”

“…However, one drawback for recognition of these transformed in vitro progeny cells is that they are not readily recognizable by mitotic errors in early beginning proliferation. The best markers are prophase divisions (Figure 2(L), Figure 2(M)) directly into anaphase [12], also an occurrence for budding yeast [75], and that endo-derived diploid cells can be perpendicularly oriented to the cytoskeleton axis [14]. Clearer notice of transformed cell-growth was apparent in extended proliferation (Figure 3(A), Figure 3(B)), when the patterns of growth were hyperplastic-like and multi-layered focal areas with cell polarity and nuclear morphology changes were present [76].…”

“…From discussions of Barrett's esophageal disease, "pathological mitosis" [22] [23] and recent demonstration of ovarian giant cells with genome reductive behavior [77] there is now good evidential material for the conclusion that endopolyploidy can act as initiator of tumorigenesis. The carcinogen-free inducing system is experimentally simple, repeatable, and well proven to change normal, diploid human cells to pre-neoplasia-like GPA [12]- [14], which next hopefully will be molecularly analyzed for genetic determinants of this GPA. Such knowledge of involved genes, never before available without "contamination" from genomic changes induced by carcinogens, has high probability of significant contributions to a cancer-preventive vaccine-program.…”