Koltsova Alla S, Pendina Anna A, Malysheva Olga V, Trusova Ekaterina D, Staroverov Dmitrii A, Yarmolinskaya Maria I, Polenov Nikolai I, Glotov Andrey S, Kogan Igor Yu, Efimova Olga A
D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 St. Petersburg, Russia.
Int J Mol Sci. 2024 Dec 26;26(1):96. doi: 10.3390/ijms26010096.
In the present study, we aimed to investigate intratumoral karyotype diversity as well as the estrogen/progesterone effect on the cytogenetic profile of uterine leiomyomas (ULs). A total of 15 UL samples obtained from 15 patients were cultured in the media supplemented with estrogen and/or progesterone and without adding hormones. Conventional cytogenetic analysis of culture samples revealed clonal chromosomal abnormalities in 11 out of 15 ULs. Cytogenetic findings were presented by simple and complex chromosomal rearrangements (64% and 36% of cases, respectively) verified through FISH and aCGH. In most ULs with complex chromosomal rearrangements, the breakpoints did not feature clusterization on a single chromosome but were evenly distributed across rearranged chromosomes. The number of breakpoints showed a strong positive correlation with the number of rearranged chromosomes. Moreover, both abovementioned parameters were in a linear dependency from the number of karyotypically different clones per UL. This suggests that complex chromosomal rearrangements in ULs predominantly originate through sequential events rather than one hit. The results of UL cytogenetic analysis depended on the presence of estrogen and/or progesterone in the culture medium. The greatest variety of cytogenetically different cell clones was detected in the samples cultured without hormone supplementation. Their counterparts cultured with progesterone supplementation showed a sharp decrease in clone number, whereas such a decrease induced by estrogen or estrogen-progesterone supplementation was insignificant. These findings suggest that estrogen-progesterone balance is crucial for forming a UL cytogenetic profile, which, in turn, may underlie the unique response of the every karyotypically abnormal UL to medications.
在本研究中，我们旨在调查肿瘤内的核型多样性以及雌激素/孕激素对子宫平滑肌瘤（ULs）细胞遗传学特征的影响。从15名患者身上获取了总共15个UL样本，分别在添加了雌激素和/或孕激素的培养基以及未添加激素的培养基中进行培养。对培养样本进行的传统细胞遗传学分析显示，15个UL中有11个存在克隆性染色体异常。细胞遗传学结果通过简单和复杂的染色体重排呈现（分别占病例的64%和36%），这些重排通过荧光原位杂交（FISH）和阵列比较基因组杂交（aCGH）得到验证。在大多数具有复杂染色体重排的UL中，断点并非集中在单一染色体上，而是均匀分布在重排的染色体上。断点的数量与重排染色体的数量呈强正相关。此外，上述两个参数与每个UL中核型不同的克隆数量呈线性相关。这表明UL中的复杂染色体重排主要源于一系列连续事件，而非单次事件。UL细胞遗传学分析的结果取决于培养基中雌激素和/或孕激素的存在。在未添加激素的培养基中培养的样本中检测到的细胞遗传学不同的细胞克隆种类最多。添加孕激素培养的样本中克隆数量急剧减少，而添加雌激素或雌激素 - 孕激素培养导致的克隆数量减少则不显著。这些发现表明，雌激素 - 孕激素平衡对于形成UL细胞遗传学特征至关重要，而这反过来可能是每个核型异常的UL对药物产生独特反应的基础。
