Department of Obstetrics and Gynecology, University of Tartu, Tartu, Estonia.
Hum Reprod. 2012 Jun;27(6):1857-64. doi: 10.1093/humrep/des125. Epub 2012 Apr 3.
De novo somatic copy number aberrations (SCNAs) in eutopic and ectopic endometria are thought to be involved in the pathogenesis of endometriosis. In this study we used, for the first time, high-density single nucleotide polymorphism-array technology for accurate detection of SCNAs, inherited DNA copy number variations (CNVs) and copy-neutral loss of heterozygosity (cn-LOH) patterns in patients with endometriosis.
The Illumina HumanOmniExpress array was used to detect de novo somatic genomic alterations in eutopic and ectopic endometria from 11 women (eight with Stage I-II endometriosis and three with Stage III-IV endometriosis) by comparatively analysing DNA from peripheral blood, eutopic endometrium and a pure population of endometriotic cells harvested from endometriotic lesions by laser capture microdissection (LCM). The frequency of the CNV in 3p14.1 from blood DNA of 187 endometriosis patients (94 with Stage I-II endometriosis and 93 with Stage III-IV endometriosis) and 171 healthy women from the Estonian general population was evaluated.
Analysis of array data showed that LCM DNA can be used successfully for detection of genetic changes as all inherited CNVs were identified in all tissues studied. No unique SCNAs or cases of cn-LOH were found in either eutopic or ectopic endometrium when compared with blood DNA. The frequency of the deletion allele in 3p14.1 did not differ between studied groups.
In the present study no endometriosis-specific SCNAs or regions of cn-LOH in eutopic or ectopic endometrium were found. Nevertheless, as we studied only 17 endometriotic tissues derived from 11 patients we cannot entirely exclude the occurrence of rare SCNAs. Based on our results we suggest that molecular mechanisms other than chromosomal rearrangements most likely underlie the onset and progression of endometriosis.
人们认为，在位和异位子宫内膜中的新生体细胞拷贝数异常（SCNAs）与子宫内膜异位症的发病机制有关。在这项研究中，我们首次使用高密度单核苷酸多态性芯片技术，准确检测了子宫内膜异位症患者在位和异位子宫内膜中的新生 SCNAs、遗传 DNA 拷贝数变异（CNVs）和拷贝中性杂合性丢失（cn-LOH）模式。
通过比较外周血、在位子宫内膜和通过激光捕获显微切割（LCM）从子宫内膜异位病变中采集的纯子宫内膜异位细胞的 DNA，使用 Illumina HumanOmniExpress 芯片检测 11 名女性（8 名患有 I-II 期子宫内膜异位症，3 名患有 III-IV 期子宫内膜异位症）在位和异位子宫内膜中的新生体细胞基因组改变。评估了 187 名子宫内膜异位症患者（94 名患有 I-II 期子宫内膜异位症，93 名患有 III-IV 期子宫内膜异位症）和 171 名来自爱沙尼亚普通人群的健康女性血液 DNA 中 3p14.1 处 CNV 的频率。
芯片数据分析表明，LCM DNA 可成功用于检测遗传变化，因为在所研究的所有组织中均鉴定出所有遗传 CNVs。与血液 DNA 相比，在位和异位子宫内膜中均未发现独特的 SCNAs 或 cn-LOH 病例。3p14.1 缺失等位基因的频率在研究组之间没有差异。
在本研究中，未发现在位和异位子宫内膜中存在子宫内膜异位症特异性 SCNAs 或 cn-LOH 区域。然而，由于我们仅研究了 11 名患者的 17 个子宫内膜异位组织，因此不能完全排除罕见 SCNAs 的发生。基于我们的结果，我们认为，除了染色体重排之外，其他分子机制很可能是子宫内膜异位症发病和进展的基础。
