Are some breast carcinomas polyclonal in origin?

Abstract

This editorial comments on the important study by Going et al. published in the present issue of the Journal [1]. Using a molecular genetic assay based on the X-chromosome inactivation principle, they found that 4 out of 12 breast carcinomas examined exhibited what the authors call "clonal mosaicism" that is, two or more monoclonal samples were mosaic (polyclonal) in respect of X chromosome inactivation between separate, morphologically homogeneous tumour areas. The authors very carefully discuss potential methodological errors that could have led to this surprising finding, which seems to run counter to the almost unanimously held conviction that carcinomas are monoclonal in origin, but none of these potential errors would explain the results. As often in such situations, the authors prudently state that further studies using independent analytical techniques are necessary to find out whether a significant proportion of mammary carcinomas are indeed polyclonal. However, there already exists a substantial body of evidence from cytogenetic studies of breast cancers indicating that many of them are polyclonal. Although there is still room for interpretation and some doubt remains as to exactly which role should be ascribed to the observed clonal heterogeneity in our models of carcinogenesis, it seems obvious that more attention than before ought to be paid to this now well documented fact.