Abstract
Today, cancer-patients can seek individual genomic tailored therapy, but at escalating costs. However, cancer-incidence reduction would reduce such health-cost. The essence of this report is a cell-culture experimental approach for the production of genetically unstable cells from normal cells which with accumulation of “mutations” might reveal early, neoplastic-like pathology. Summarily the experimental focus was on: 1) establishment of a simple nutritional method (amino acid deprivation) for young-cell-response with depoly-ploidization of endopolyploid cells to diploid CIN-cells, 2) a first time observation of a fast growing new, small cell-type, appearing time-correlated with haploid segregations in normal, fibroblast metaphases and 3) growth characteristics of the progeny cells in 1) and 2) which from their young-cell derivation, could be growth-extended in cultural passages. This would hypothetically model early tumorigenic progression from normal cells. These studies revealed gain of proliferative advantage (GPA), multilayered, changed patterns of growth, focal 3-D cell-heaps with cell polarity change, and star-like mitotic forms. Comparatively, these developments were typical of hyperplasias. The transiency of the originating genome reductive mechanisms may have prevented earlier detections. It is discussed that present growth-changes were responses to homozygous-caused loss of heterozygosity (LOH) of putative pro-proliferation genetics, whereas leukemic and some solid tumor cells showed hemizygous-caused LOH in near-haploid clonal proliferations. The practical outcome is an experimentally simple, nutrition-based model system for SNP-based haplo-karyotyping of the two aberrant cell-types with GPA, which is a cancer, fundamental trait. Never before have cellular mechanism been shown to initiate in normal, human cells, neoplastic-like proliferative responses.
Highlights
Mitotic karyology is presently a complementing method to karyology by single-nucleotide-polymorphism (SNP) array studies in tumorigenesis (Yang et al, 2011, Fan et al, 2011; Peters et al, 2012)
The results showed hyperplastic-like growth from both cell-types with changed growth patterns associated with focal three dimensional (3-D) growths
The present study used WI-38 cells to verify amino acid deprivation (AAD) responses of L645-cells, and most of the illustrative material was selected from comparing photographs, which often, L645- cells showed with greater clarity
Summary
Mitotic karyology is presently a complementing method to karyology by single-nucleotide-polymorphism (SNP) array studies in tumorigenesis (Yang et al, 2011, Fan et al, 2011; Peters et al, 2012). SNP has the advantage of interphase cell-use and of resolving “cryptic” genomic changes such as single nucleotide change, small deletions and duplications, and whole chromosomal and segmental uni-parental disomy (UPD) with homozygous-caused loss of heterozygosity (LOH) (Fitzgibbon et al, 2005; Gondek et al, 2008). Does this mean that cytogenetics in the near future will be even more passé than it has already become? These latter data can disclose therapy-relevant pathways and www.ccsenet.org/cco
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