CHROMOSOME INACTIVATION IN THE NORMAL FEMALE GENITAL-TRACT - IMPLICATIONS FOR IDENTIFICATION OF NEOPLASIA

Monoclonal proliferative lesions mag be identified by X chromosome ina ctivation skewing relative to normal polyclonal tissues. We have quant itatively analyzed X-inactivation patterns throughout polyclonal uteri ne tissues to develop interpretive criteria for recognition of monoclo nal neoplasms. Six fresh tissue samples (two samples each of cervix, e ndometrium, and myometrium) were collected from hysterectomy specimens , and the percentage of androgen receptor (HUMARA) marker allele prese nt on inactive X chromosomes was calculated from a PCR assay. Exact ba lancing yields 50% of the marker on the inactive X, whereas complete s kewing shows either 0 or 100%. X inactivation was similar throughout t he tissues of each uterus but was significantly different among the 11 women studied. Comparison of differences in X inactivation between pa irs of polyclonal tissue samples within each uterus (Xi spread) permit ted delineation of cumulative experimental and biological variation of this parameter. Polyclonal-polyclonal Xi spread averaged 10.7 and was independent of the tissue type, sampling site, or the individual stud ied. Severe baseline skewing of reference polyclonal tissues or contam ination of monoclonal tissue by polyclonal cells may reduce the polycl onal-monoclonal Xi spread. The extent of X-inactivation skewing necess ary to infer a monoclonal process should exceed the 20 or 27 point spr ead seen, respectively, between 85 and 95% of polyclonal samples.