ANALYSIS OF ANDROGEN RECEPTOR DNA REVEALS THE INDEPENDENT CLONAL ORIGINS OF UTERINE LEIOMYOMATA AND THE SECONDARY NATURE OF CYTOGENETIC ABERRATIONS IN THE DEVELOPMENT OF LEIOMYOMATA
ANALYSIS OF ANDROGEN RECEPTOR DNA REVEALS THE INDEPENDENT CLONAL ORIGINS OF UTERINE LEIOMYOMATA AND THE SECONDARY NATURE OF CYTOGENETIC ABERRATIONS IN THE DEVELOPMENT OF LEIOMYOMATA
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DOI：
10.1002/gcc.2870110102
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发表时间：
1994-09-01
影响因子：
3.7
通讯作者：
SKLAR, J
中科院分区：
文献类型：
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作者：
MASHAL, RD;FEJZO, MLS;SKLAR, J
子宫平滑肌瘤被认为是单克隆肿瘤。因此，用G6 PD同种型作为X染色体失活的标志物对克隆性的研究表明，单个子宫内的多个肿瘤具有独立的起源。然而，最近的一项研究评估了活性和非活性X染色体DNA之间的甲基化差异，结果表明多个肿瘤可能源于一个共同的前体。我们通过分析X染色体失活（由X连锁雄激素受体基因甲基化状态指示），检测了来自16例患者的36例平滑肌瘤的克隆性。如该试验所示，所有提供信息的平滑肌瘤均为单克隆来源。在多发性平滑肌瘤患者中，X同源物之间的失活随机分布，与每个肿瘤的独立起源一致。还对36个肿瘤中的27个进行了短期细胞培养的细胞遗传学分析。在两个肿瘤中的每一个都有克隆核型异常的细胞和核型正常的细胞，从短期培养物中制备的DNA显示出与平滑肌瘤相同的X失活的单克隆模式。这些数据表明，核型正常的细胞存在于短期培养的子宫平滑肌瘤是肿瘤克隆的一部分，肿瘤细胞的克隆性扩增先于细胞遗传学畸变的发展。(C)1994 Wiley-Liss，Inc.
Uterine leiomyomata are thought to be monoclonal neoplasms. Accordingly, investigations of clonality with G6PD isoforms used as a marker for X chromosome inactivation have suggested independent origins for multiple tumors within individual uteri. However, results from a recent study assessing methylation differences between DNA of active and inactive X chromosomes have been interpreted to suggest that multiple tumors may arise from a common precursor. We have examined the clonality of 36 leiomyomata from 16 patients by analyzing X chromosome inactivation as indicated by the methylation status of the X-linked androgen receptor gene. As shown by this assay, all informative leiomyomata were monoclonal in origin. In patients with multiple leiomyomata, a random distribution of inactivation between the X homologs was noted, consistent with an independent origin of each tumor. Cytogenetic analysis was also performed on short-term cell cultures of 27 of the 36 tumors. In each of two tumors that had both cells with a clonal karyotypic abnormality and karyotypically normal cells, DNA prepared from short-term cultures showed a monoclonal pattern of X inactivation identical to that of the leiomyoma from which they were derived. These data suggest that karyotypically normal cells present in short-term cultures of uterine leiomyomata are part of the tumor clone, and that clonal expansion of tumor cells precedes the development of cytogenetic aberrations. (C) 1994 Wiley-Liss, Inc.