TITLE:
Cancer Prevention? Fundamental Genomic Alterations Are Present in Preneoplasia, Including Function of High Frequency Selected Mutations (HFSMs)
AUTHORS:
Kirsten H. Walen
KEYWORDS:
DNA/Breakage/Repair, Mitotic Slippage, Cohesin, Tetraploid System, Segregation/Orderly, Hyperplasia, Dysplasia, 4n-Cell-Cycles, Skewed Cytoskeleton, Antibody, CRISPR-Caspase, Therapy
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.7 No.6,
June
23,
2016
ABSTRACT: In a series of publications a special, tetraploid diplochromosomal division system to only two types of progeny cells (4n/4C/G1 and 2n/4C
para-diploid) has been suggested to initiate preneoplasia that can lead to a
cancerous pathway. Colorectal and other preneoplasia are known with the
pathogenic, histological phases of hyperplasia to arrested adenoma/nevi that
can give rise to dysplasia with high risk for cancer development. The present
theme is to find solutions to tumorigenic unsolved, biological problems
(queries), explainable from the tetraploid 4n-system, which would support its
operation in the cancerous pathway. Presently admitted, the mutational sequencing
of the cancer genome (cancer chemistry) cannot discover so-called “dark
matter”, which herein is considered to be the queries. The solutions from the
4n-system were largely supported by mutated APC-induced same type of
tetraploidy from the mitotic slippage process. But importantly, these behaviors
and consequences could be linked to the beginning of hyperplastic lesions and
their development to the arrest-phase of preneoplasia (polyps/nevi). Function
of HFSMs is mostly unknown, but for Barrett’s esophagus, HFSMs (p53, p16ink4a)
caused inactivation of the Rb gene, leading to dysplasia with 4n, aneuploid,
abnormal cell cycles. In vitro models
of the 4n-system from normal human cells
recapitulated preneoplasia-like histopathological changes. It was speculated that the “cancer-crucial” step
to dysplasia could be therapy-vulnerable to CRISPR-caspase editing, and
perhaps antibody treatment. Additionally, the 4n-system with spontaneous
cell-behaviors together with preneoplasia molecular data promises construction
of a more truthful cancer-paradigm than from sequencing data alone.