(LAM) Gene Mutation Screening And Plasma Free DNA Detection And Nodular Sclerosis (TSC) Lung Performance Summary And Analysis

Part I:Screening of genetic mutation in lung tissues and detection of genetic mutation in circulating tumor DNA of patients of lymphangioleiomyomatosis (LAM)Objectives:To investigate the usefulness of personalized screening of genetic mutation of tumor driver genes in patients of LAM, with the exploration of the usage of genetic mutation screening in finding new therapeutic targets. To investigate the usefulness of circulating tumor DNA (ctDNA) in the molecular diagnosis of LAM.Methods:We included 10 LAM patients that visited Peking Union Medical College Hospital from October 2015 to May 2016. The tissues were achieved via transbronchial lung biopsy (TBLB) or open lung biopsy or from the operations/interventions in the past medical history. The clinical information, including medical history, imaging examination of chest and abdomen and serum vascular endothelial growth factor D (VEGF-D) was collected. We also reviewed the pathological diagnoses of the patients, including morphology and immunohistochemical test (SMA and HMB-45). For each patient, 10mL of blood was extracted for preparation of plasma DNA and white blood cells. The screening of genetic mutation in the tissues was via next generation sequencing and after that the specific primers were designed and used for detection of mutation in ctDNA.Results:We found 8 mutations if TSC2 among 6 patients, and the mutation frequencies in the tissue were 2.10-47.60%. The detection of TSC2 mutation was generally consistent with the clinical diagnosis and pathological diagnosis. We found no TSC mutations in 3 patients but mutations in other cancer driver genes (FGF23, KMT2C, FZR1 and NOTCH2). The mutation frequencies in ctDNA were 0.0005-0.0164%.Conclusions:Personalized mutation screening in the tissues might be useful in the molecular diagnosis of LAM and finding new therapeutic targets. But the mutation frequency in the ctDNA was low, so the effects of ctDNA in diagnosis of LAM needs further investigation.Part â…¡:Features of pulmonary involvement of 22 tuberous sclerosis complex (TSC) cases in Peking Union Medical College HospitalObjectives:To assess the clinical manifestations of pulmonary involvement of TSC, including symptoms and imaging tests.Methods:We analyzed the clinical records of 22 cases who visited Peking Union Medical College Hospital from Oct 2015 to Jun 2016. We focused on pulmonary manifestation, including lymphangioleiomyomatosis (LAM) and multifocal micronodular pneumocyte hyperplasia (MMPH).Results:9 out of 22 patients (40.9%) had chest imaging test consistent with LAM, including 1 male and 8 female patients.13 of 22 patients (59.1%) had multiple pulmonary nodules, including 7 males and 6 females.8 patients (36.4%) had pulmonary symptoms during medical histories, including 2 males and 6 females. Multiple pulmonary nodules were not significantly related with gender and respiratory symptoms. LAM is significantly correlated with gender and respiratory symptoms. We identified 3 patients that had follow-up chest imaging test, which showed that pulmonary nodules resolved during treatment with rapamycm.Conclusions:Chest imaging test is important in the evaluation of pulmonary involvement of TSC. Rapamycin might have effects in treating multiple pulmonary nodules.