In the present study, we aimed to check whether uterine leiomyomas (ULs) with an apparently normal karyotype in vitro comprise “hidden” cell subpopulations with numerical chromosome abnormalities (heteroploid cells). A total of 32 ULs obtained from 32 patients were analyzed in the study. Each UL was sampled for in vivo and in vitro cytogenetic studies. Karyotyping was performed on metaphase preparations from the cultured UL samples. A normal karyotype was revealed in 20 out of the 32 ULs, of which 9 were selected for further study based on the good quality of the interphase preparations. Then, using interphase FISH with centromeric DNA probes, we analyzed the copy number of chromosomes 7 and 16 in 1,000 uncultured and 1,000 cultured cells of each selected UL. All of the ULs included both disomic cells representing a predominant subpopulation and heteroploid cells reaching a maximum frequency of 21.6% (mean 9.8%) in vivo and 11.5% (mean 6.1%) in vitro. The spectrum of heteroploid cells was similar in vivo and in vitro and mostly consisted of monosomic and tetrasomic cells. However, their frequencies in the cultured samples differed from those in the uncultured ones: while the monosomic cells decreased in number, the tetrasomic cells became more numerous. The frequency of either monosomic or tetrasomic cells both in vivo and in vitro was not associated with the presence of MED12 exon 2 mutations in the tumors. Our results suggest that ULs with an apparently normal karyotype consist of both karyotypically normal and heteroploid cells, implying that the occurrence of minor cell subpopulations with numerical chromosome abnormalities may be considered a characteristic of UL tumorigenesis. Different frequencies of heteroploid cells in vivo and in vitro suggest their dependence on microenvironmental conditions, thus providing a pathway for regulation of their propagation, which may be important for the UL pathogenesis.
Cytogenet Genome Res

中文翻译：

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具有明显正常核型的子宫平滑肌瘤包括较小的异倍体亚群，在体内和体外均代表不同的表达

在本研究中，我们旨在检查在体外看来具有正常核型的子宫平滑肌瘤（UL）是否包含具有数字染色体异常（异倍体细胞）的“隐藏”细胞亚群。在该研究中分析了从32例患者中获得的32例UL。对每个UL取样进行体内和体外细胞遗传学研究。对培养的UL样品的中期制剂进行核型分析。在32个UL中，有20个揭示了正常的核型，根据中间相制剂的良好质量，选择了9个用于进一步研究。然后，使用相间FISH与着丝粒DNA探针，我们分析了每个所选UL的1,000个未培养和1,000个培养细胞中7号和16号染色体的拷贝数。所有的UL都包括代表主要亚群的二体性细胞和异倍体细胞，它们在体内的最大频率达到21.6％（平均9.8％），在体外达到11.5％（平均6.1％）。异倍体细胞的光谱在体内和体外相似，并且主要由单体细胞和四体细胞组成。但是，它们在培养样品中的频率与未培养样品中的频率不同：虽然单体细胞数量减少，但四体细胞数量却更多。体内和体外单体或四体细胞的频率均与存在 但是，它们在培养样品中的频率与未培养样品中的频率不同：虽然单体细胞数量减少，但四体细胞数量却更多。体内和体外单体或四体细胞的频率均与存在 但是，它们在培养样品中的频率与未培养样品中的频率不同：虽然单体细胞数量减少，但四体细胞数量却更多。体内和体外单体或四体细胞的频率均与存在肿瘤中的MED12外显子2突变。我们的研究结果表明，具有正常核型的ULs由核型正常细胞和异倍体细胞组成，这意味着出现具有数字染色体异常的次要细胞亚群可能被认为是UL肿瘤发生的特征。体内和体外异倍体细胞的不同频率表明它们对微环境条件的依赖性，从而提供了调节其繁殖的途径，这可能对UL发病机理很重要。
细胞遗传基因组研究