Embryonic reversions and lineage infidelities in tumour cells: genome-based models and role of genetic instability

Reversions to 'embryonic precursor'-type cells and infidelities of tumour cell lineage (including metaplasias) have been recognized as aspects of various tumour types since the 19th century. Since then, evidence of these phenomena has been obtained from numerous clinical, biochemical, immunological and molecular biological studies. In particular, microarray studies have suggested that 'aberrant' expressions of relevant genes are common. An unexplained aspect of the results of these studies is that, in many tumour types, the embryonic reversion or lineage infidelity only occurs in a proportion of cases. As a parallel development during the molecular biological investigation of tumours over the last several decades, genetic instability has been found much more marked, at least in some preparations of tumour cells, than that identified by means of previous karyotypic investigations of tumours. This study reviews examples of embryonic reversion and lineage infidelity phenomena, which have derived from the various lines of investigation of cancer over the last 150 or so years. Four categories of circumstances of the occurrence of embryonic reversions or lineage infidelities have been identified - (i) as part of the defining phenotype of the turnout, and hence being presumably integral to the tumour. type, (ii) present ab initio in only some cases of the tumour type, and presumably being regularly associated with, but incidental to, the essential features of the tumour type, (iii) occurring later in the course of the disease and thus being possibly a manifestation of in vivo genetic instability and 'tumour progregsion' and (iv) arising probably by genetic instability, during the processes, especially cell culture, associated with ex vivo investigations. Genomic models are described which might account for the origin of these phenomena in each of these circumstances.