Different mutation profiles between epithelium and stroma in endometriosis and normal endometrium
Different mutation profiles between epithelium and stroma in endometriosis and normal endometrium
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DOI：
10.1093/humrep/dez155
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发表时间：
2019-10-01
影响因子：
6.1
通讯作者：
Enomoto, Takayuki
中科院分区：
文献类型：
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作者：
Suda, Kazuaki;Nakaoka, Hirofumi;Enomoto, Takayuki
研究问题：在卵巢癌组织和正常子宫内膜的上皮细胞和基质细胞之间是否存在共同的突变谱？总结回答：我们的研究揭示了卵巢增生组织和正常子宫内膜中的上皮细胞和基质细胞之间没有共同的突变。已知：卵巢增生组织和正常子宫内膜中的上皮细胞都具有癌症相关基因的体细胞突变，如磷脂酰肌醇-4，5-二磷酸3-激酶催化亚基α（PIK 3CA）和KRAS原癌基因GT3（KRAS）。研究设计、规模、持续时间：我们进行了一项回顾性研究，以确定子宫内膜异位症组织和正常子宫内膜基质细胞的突变谱。我们收集了11个子宫内膜异位症间质样本和10个正常子宫内膜间质样本之间的2013年和2017年在三级care.PARTICIPANTS/材料，设置，方法：激光显微切割方法是用来获得卵巢子宫内膜异位症和/或其他非侵入性妇科疾病患者的卵巢子宫内膜异位症和正常子宫内膜组织中的间质细胞。进行靶基因测序以评估和比较基质细胞与我们先前研究中获得的上皮细胞的突变谱。对于靶基因测序，基于先前对卵巢子宫内膜异位症、正常子宫内膜、子宫内膜异位症相关的卵巢癌和子宫内膜癌的基因组分析选择76个基因。卵巢上皮性腺瘤和正常子宫内膜间质中的突变体（11个子宫内膜异位症样本中有18个突变，10个正常子宫内膜样本中有16个突变），但与配对上皮样本没有任何突变。间质样本的突变等位基因频率显著低于卵巢上皮性腺瘤（P = 6.0 × 10 ~（-11））和正常子宫内膜（P = 1.4 × 10 ~（-7））的上皮样本。此外，体细胞突变在间质细胞中的功能作用仍不清楚。更广泛的意义的发现：不同的突变谱之间配对上皮细胞和间质细胞在卵巢腺瘤和正常子宫内膜表明，上皮细胞和间质细胞的起源将是相互独立的，在正常子宫内膜和卵巢腺瘤;然而，上皮间质转化的理论被提出在卵巢腺瘤。
STUDY QUESTION: Are there common mutation profiles between epithelial and stromal cells in ovarian endometriotic tissue and the normal endometrium?SUMMARY ANSWER: Our study revealed no common mutations between epithelial and stromal cells in ovarian endometriotic tissue and the normal endometrium.WHAT IS KNOWN ALREADY: Epithelial cells in both ovarian endometriotic tissue and the normal endometrium harbor somatic mutations in cancer-associated genes such as phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and KRAS proto-oncogene, GTPase (KRAS).STUDY DESIGN, SIZE, DURATION: We performed a retrospective study to identify the mutation profiles of stromal cells in endometriotic tissue and the normal endometrium. We collected 11 endometriotic stroma samples and 10 normal endometrial stroma samples between 2013 and 2017 at a tertiary care center.PARTICIPANTS/MATERIALS, SETTING, METHODS: The laser microdissection method was used to obtain stromal cells in ovarian endometriotic and normal endometrial tissues from patients with ovarian endometriosis and/or other non-invasive gynecological diseases. Target gene sequencing was performed to assess and compare the mutation profiles of stromal cells with those of epithelial cells obtained in our previous study. For target gene sequencing, 76 genes were selected based on previous genomic analyses for ovarian endometriosis, normal endometnum, endometriosis-related ovarian cancer and endometrial cancer.MAIN RESULTS AND THE ROLE OF CHANCE: Stromal samples in ovarian endometrioma and normal endometrium harbor somatic mutations (18 mutations in 11 endometriosis samples and 16 mutations in 10 normal endometrial samples) but did not share any mutations with paired epithelial samples. The mutant allele frequency of stromal samples was significantly lower than that of epithelial samples in ovarian endometrioma (P = 6.0 x 10(-11)) and normal endometrium (P = 1.4 x 10(-7)).LIMITATIONS, REASONS FOR CAUTION: The number of genes evaluated in the mutational analysis was limited. Additionally, the functional roles of somatic mutations in stromal cells remain unclear.WIDER IMPLICATIONS OF THE FINDINGS: Different mutation profiles between paired epithelial and stromal cells in both ovarian endometrioma and normal endometrium suggest that origins of epithelial and stromal cells would be independent of each other in both normal endometrium and ovarian endometrioma; however, the theory of epithelial-mesenchymal transition is proposed in ovarian endometrioma.