Clonal origins of human endometrial cancer

ABSTRACT

The aim of this study was to analyze the X inactivation in DNA extracted from microdissected endometrial carcinoma by Hpa II restriction and PCR of the androgen receptor exon I CAG polymorphism. The results revealed that monoclonality was confirmed in 105/133 samples of carcinoma cells from 31/32 informative endometrial cancers. Clonality was identical in seven cases. Unexpectedly, four of twelve cancers with two or more monoclonal samples available were mosaic [polyclonal] in respect of X chromosome inactivation between morphologically homogeneous tumor cell samples. It was concluded that concordant clonality supports a common clonal origin of high grade and low grade endometrial cancers, but frequent mosaic X inactivation in endometrial cancer cannot be explained by non-tumor cell contamination. These carcinomas are probably multiclonal. Possible mechanisms include simultaneous transformation of cell groups straddling X chromosome inactivation, or recruitment of bystander stem cells by DNA transfer from necrotic or apoptotic tumor cells