子宫内膜异位症是常见妇科疾病，但至今病因未明，诊断滞后于发病多年，手术及药物治疗均易复发。我们在前期实验中运用外显子测序(WES)技术对在位、异位内膜腺体细胞进行了测序，发现了大量潜在的突变位点和致病基因。本研究拟采用双线研究的手段，运用高通量测序技术结合激光显微切割技术从DNA、RNA两个层面探寻致病基因及相关信号通路。研究内容：1）采用直接测序法对大量样本进行前期WES结果的验证，确定突变位点；2）转录组测序技术量化在位、异位内膜腺体细胞中异常表达的mRNA和lncRNA，获得疾病特异性表达谱；3）联合转录组测序和WES的结果准确定位致病基因及相关信号通路，并采用实时定量PCR、原位杂交等技术扩大样本量进行验证。本研究对揭示内异症基因层面的发病机制具有重要意义，为诊断标记物及个体化靶向治疗位点的选择提供思路。

Endometriosis is considered to be a common gynecologic disease; however, the key drivers of endometriosis pathogenesis remain poorly understood, the diagnosis lags behind the onset for many years, and the treatments of drug therapy and surgery make this disease easily recur. In previous study, we conducted whole-exome sequencing (WES) to comprehensively search for somatic mutations in both eutopic and ectopic endometrium and identified many candidate single nucleotide variants and genes. Based on these observations, we propose using high through-put sequencing combined with laser capture microdissection to pinpoint the endometriosis-causing genes in the levels of DNA and RNA simultaneously. In this study, we will: 1) use PCR-direct sequencing method to verify the mutations discovered in previous WES in large sample size; 2) use RNA sequencing method to quantify the mRNA and lncRNA expressions level and to analysis potential genes; 3) integrate WES data with RNA sequencing data, localize the disease-related genes precisely and use transcriptomic methods, like real time PCR and in situ hybridization, to verify the data. Our study has important significance and value in revealing the pathogenesis of endometriosis and finding early diagnostic biomarkers and effective target therapies.