Epithelial carcinogenesis: challenging monoclonality

How carcinomas begin remains unclear, but experimental data do not entirely exclude the participation of more than one clone of neoplastic cells, even in relatively advanced epithelial tumour growth. Microdissection and new PCR clonality assays exploiting X-linked polymorphisms, some of which (including XIST) are expressed in RNA, create investigational opportunities complementary to other molecular analyses, but a reliable in situ assay of X-inactivation remains desirable. The necessity for stringent controls in clonality analysis is emphasized. While it may be possible to reconcile 'pluriclonal' (oligoclonal or polyclonal) carcinogenesis with widely accepted paradigms of genetic/epigenetic change and clonal selection in epithelial neoplasia, it deserves critical study as novel carcinogenic mechanisms would be implied.