A proposal that malignancies represent genetic changes in cell surface RNA.

Abstract

A great number of experimental studies have now been performed with malignant cells. The mass of data generated presents a confusing and often apparently contradictory picture of the fundamental molecular biological defect which most scientists sense must be the cause of transformation of a normal cell into a malignant one. This paper proposes the hypothesis that RNA on the exterior of the cell membrane organizes the various functional molecular aggregates such as transport complexes (permeases), lectin receptor sites, transmembrane microfilament attachment sites, hormone receptor complexes, and the elusive contact inhibition components. Furthermore it is proposed that a defect in the production of or competition for the assembly of exterior-organizer RNA (exoRNA) complexes is the primary molecular defect inherent in all malignancies. The defect could be caused by deletion of a chromosome region producing or controlling exoRNA, mutation of the genes involved in exoRNA production or by insertion of viral genetic material into the genome thereby producing an incomplete viral RNA (vRNA) which competes for exoRNA binding sites in cell surface complexes. Such changes would be genetically transmitted and could represent a range of genetic change between chromosomal deletion and point mutation. Several experiments are suggested to directly test the hypothesis.