Fields and field cancerization: The preneoplastic origins of cancer

Abstract

Most basic research on cancer concerns genetic changes in benign and malignant tumors. Yet evidence indicates that the majority of the mutations in tumors occur in the preneoplastic field stage of their development. That early stage is represented by grossly invisible, broad regions of "field cancerization" which have not, heretofore, been operationally analyzed in cell culture. Conditions are described for quantitating preneoplasia by increased saturation density followed by progression to transformation. These parameters are driven by Darwinian selection of spontaneously occurring, cumulative mutations, in accordance with recent genomic analyses of human cancer, just as it is in the evolution of species. The cell culture model will allow correlation of the preneoplastic increases in saturation density with genetic changes, and development of methods for demarcating fields during surgery so that they can be excised along with the tumor, thereby reducing the possibility of recurrence at the site.

Role of DNA methylation in head and neck cancer

“…Genetic evidence indicates that the majority of squamous HNC originate from hyperplastic fields characterized by higher numbers of proliferating cells and clonal selection (Rubin 2011; Tabor et al 2002). Almost two thirds of the tumor recurrences following resection occur in these regions (Tabor et al 2004; Ha and Califano 2003).…”

The Role of Chromosome Missegregation in Cancer Development: A Theoretical Approach Using Agent-Based Modelling

“…At this point, the population is made up of descendants of many of the cells present in the initial population used to seed the simulation, but is dominated by a small number of related but genetically heterogeneous aggressive cell clones, as in human cancers [29]. The population also includes cells poised in a pre-cancerous state that are the product of a process analogous to field cancerization [30] which occurs as cells compete for space during the course of simulations. These pre-cancerous cells will be likely be related by lineage to the aggressive sub-clones that constitute the bulk of the tumour.…”

“…Although on average a dramatic shift towards diploidy of a given chromosome can be observed, the spread of the results point to a large number of cases where surgery leads to the total loss of tumour suppression (with intact diploid division genes), an accelerated gain in oncogenes (with normal levels of tumour suppression) or a lethal combination of both. This leads to variability in the outcomes of surgery that depend on the limits of the cell population removed [29], and the extent of field cancerization in the tissue [30]. These subtle but complex dynamics in surgery are best observed on a case-by-case examination of the evolved genotypes, as those shown in Figure 3 B and Figure 3 C.…”

Systems biology of cancer: entropy, disorder, and selection-driven evolution to independence, invasion and “swarm intelligence”

“…, independence: (1) sustaining proliferation signaling: It involves proliferation as a unicellular organism, without need of initiation by a physiological growth factor, and evading of growth suppressors and loss of contact inhibition [89]; (2) activating invasion involves the relief of physiological tissue constrains, cell–cell adhesion, polarity, anoikis, etc . This relief, which may involve genetic or epigenetic events [90], is also described as field cancerization [91]. It is therefore interesting that the Warburg type of glucose channeling into non-oxidative metabolism confers resistance to anoikis [92].…”