Human tumour clonality assessment—flawed but necessary

Abstract

One of the premises of the somatic mutation theory of carcinogenesis is that tumours are clonal lesions derived from a single mutated stem cell progenitor. This theory spawned a proliferation of clonality studies, using a variety of different molecular markers to try to determine tumour clonality in multiple organs. In order to establish true clonality, it is necessary to identify the original founding mutation that occurred at the initiation of the progenitor clone. Use of other lesions may only serve to identify sub-clones. As founding mutations have not been properly established in many organ systems, human clonality assessments carry this caveat. However it is only through clonality and mutation burden assessments that phylogenetic tress become established. Here, we review the advantages, disadvantages and use of different clonality markers.