Fields and field cancerization: The preneoplastic origins of cancer

Asymptomatic hyperplastic fields are precursors of neoplasia, and their progression to tumors can be tracked by saturation density in culture

Authors

  • Harry Rubin

    Corresponding author
    1. Department of Molecular and Cell Biology, Life Sciences Addition, University of California, Berkeley, CA, USA
    • Department of Molecular and Cell Biology, Life Sciences Addition, University of California, Berkeley, CA 94720, USA.
    Search for more papers by this author

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.

Ancillary