Mutter G L, Boynton K A
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Cancer Res. 1995 Nov 1;55(21):5080-4.
Monoclonal proliferative lesions may be identified by X chromosome inactivation skewing relative to normal polyclonal tissues. We have quantitatively analyzed X-inactivation patterns throughout polyclonal uterine tissues to develop interpretive criteria for recognition of monoclonal neoplasms. Six fresh tissue samples (two samples each of cervix, endometrium, and myometrium) were collected from hysterectomy specimens, and the percentage of androgen receptor (HUMARA) marker allele present on inactive X chromosomes was calculated from a PCR assay. Exact balancing yields 50% of the marker on the inactive X, whereas complete skewing shows either 0 or 100%. X inactivation was similar throughout the tissues of each uterus but was significantly different among the 11 women studied. Comparison of differences in X inactivation between pairs of polyclonal tissue samples within each uterus (Xi spread) permitted 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 studied. Severe baseline skewing of reference polyclonal tissues or contamination of monoclonal tissue by polyclonal cells may reduce the polyclonal-monoclonal Xi spread. The extent of X-inactivation skewing necessary to infer a monoclonal process should exceed the 20 or 27 point spread seen, respectively, between 85 and 95% of polyclonal samples.
相对于正常多克隆组织，单克隆增殖性病变可通过X染色体失活偏斜来识别。我们对多克隆子宫组织中的X失活模式进行了定量分析，以制定识别单克隆肿瘤的解释标准。从子宫切除标本中收集了六个新鲜组织样本（宫颈、子宫内膜和肌层各两个样本），并通过聚合酶链反应（PCR）测定法计算失活X染色体上雄激素受体（HUMARA）标记等位基因的百分比。精确平衡会使失活X染色体上50%的标记出现，而完全偏斜则显示为0%或100%。每个子宫的组织中X失活情况相似，但在研究的11名女性中存在显著差异。比较每个子宫内多克隆组织样本对之间X失活的差异（Xi spread），可以描绘出该参数累积的实验和生物学变异。多克隆-多克隆Xi spread平均为10.7，且与组织类型、采样部位或所研究的个体无关。参考多克隆组织的严重基线偏斜或单克隆组织被多克隆细胞污染可能会降低多克隆-单克隆Xi spread。推断单克隆过程所需的X失活偏斜程度应分别超过85%至95%的多克隆样本中观察到的20或27个点的差值。
