A Traceable Cancer Model: DNA Damage, Fragile Site-SMGs, Mitotic Slippage, 4n-Genome-Reduction to Fitness-Gained, Initiating, 2n First Cells ()
ABSTRACT
We have known since 1976 that cancer evolves clonally from one initiated normal human cell, the first cell.
Today we see that this fact has been overshadowed from federal funding choice
of the mutation theory (MT), which not yet has shown tumorigenesis-initiation
in normal human cells. Our suggested, death signaled, stress model from time
delayed S-period (replication slowness), causing repair instability from
under-replicated lesions in repetitive DNAs, herein has the objective of
revealing, significant literature support from a mini-review. We reasoned that
early versus late S-period stress would have
different outcomes: early the slowness affecting mitotic slippage with diploid re-replication to 4n cells whereas late-S,
with milder stress effect, producing
diploid cells. In cancer burden, near-half is diploid, but tetraploid solid tumors have the attention. The initial 4n cells were special with orderly
genomic reductive division to diploid first cells with measurable fitness-gain
from hours-reduced total cell cycle time. Experimental data from Coxsakie-B3
virus infected normal fibroblasts, reiterated 4n cell production from death-signaled recovery-cells with
progressive cell-phenotypic changes to polygonal and roundness cell-shapes,
indistinguishable from diagnostic/prognostic cancer morphology. The 4n cells showed a self-inflicted 90° turn of the 4n nucleus before division, affecting a
perpendicular orientation of the fitness-gained first cells relative to
neighboring cells. In an illustrated cell cycle drawing with early and late
S-period stress, it became clear that coding genes on borders of repair
unstable satellite, repetitive DNA regions, could become mutated. We found
these mutations to be tumor SMGs (significantly mutated genes). Evidential
material was presented for loss of function genetics driving tumorigenesis to a
parasitic lifestyle.
Share and Cite:
Walen, K. (2021) A Traceable Cancer Model: DNA Damage, Fragile Site-SMGs, Mitotic Slippage, 4n-Genome-Reduction to Fitness-Gained, Initiating, 2n First Cells.
Journal of Cancer Therapy,
12, 365-386. doi:
10.4236/jct.2021.126033.