肺淋巴管肌瘤病（LAM）是一种罕见的肺部囊性疾病，与体细胞TSC2突变有关，是一种具体破坏性和转移性的低度恶性肿瘤。由于疾病罕见并且肺部标本难以获得，LAM的分子遗传学研究受到严重限制。外周血有望成为一种简便易行的用于LAM分子遗传学研究的替代来源，为个体化治疗提供关键的指导依据。本课题的目标是研究外周血LAM细胞和游离DNA的TSC2突变，并分析其与临床表型、肺功能进展和针对TSC2突变的靶向治疗的关联性。研究分为两部分。第一部分是通过自主研发的能够高效分离游离肿瘤细胞的微流控芯片平台在体外捕获循环LAM细胞，同时直接分离患者的血浆游离DNA，选用杂合性丢失检测方法检查TSC2突变状况。第二部分将系统观察40例LAM患者24个月。分析TSC2突变（阳性、阴性以及突变程度）与临床表型、疾病进展（第一秒用力呼出气量的年下降率）和针对TSC2突变的靶向治疗（西罗莫司）治疗效果的关联性。

Pulmonary lymphangioleiomyomatosis (LAM), a destructive and metastatic low-grade malignant tumor, is a rare cystic lung disease with somatic mutation on TSC2. The research of genetic characteristics of LAM requires surgical biopsy to obtain lung tissue, which is difficult to perform under many situations. Peripheral blood LAM cells and DNA would be a convenient and feasible approach to investigate the molecular biology of the disease. We aim to investigate the TSC2 gene mutation from peripheral circulating LAM cells and cell free DNA and their clinical significance in monitoring disease progress and treatment response. In the first part of the research, circulating LAM cells will be captured with a patented high-efficiency microfluidic chip. DNA will be harvested from captured LAM cells or plasma cell free DNA. Then loss of heterozygosity of TSC2 will be detected. In the second part of research, 40 cases of LAM will be systematically observed for 24 months. Clinical characteristics, rate of loss of pulmonary function, and treatment response to targeted therapy will be recorded. Then the relationship of TSC2 mutation and clinical significance will be analyzed.