Mesothelioma_and_normal_pleura

Malignant pleural mesothelioma (MPM) is an aggressive tumour of the pleural lining of the lung associated with asbestos exposure that develops over a period of 40 to 50 years. Patients often present late in disease and have a prognosis of less than 12 months. Although asbestos has been banned in developed countries the incidence of MPM is still increasing in Europe and is expected to rise across developing countries. Significant progress has been made in understanding MPM tumour biology, but there are still a number of important open questions in the field regarding the pathogenesis and evolution of MPM. Recent advances in genetic and epigenetic sequencing of benign tissue can provide insight into the earliest stages of MPM and allow reconstruction of comprehensive maps of tumour evolution. We hypothesise that MPM is the result of a decades long process of pleural cell damage and regeneration resulting acquisition of genetic and epigenetic changes over time. Whole genome, RNA, and ATAC sequencing of normal pleura, early pleural thickening and plaques from asbestos exposure, and MPM will provide critical insight into this process to inform future techniques for diagnosis and treatment of MPM.恶性胸膜间皮瘤（Malignant Pleural Mesothelioma, MPM）是一种侵袭性极强的肺部胸膜肿瘤，与石棉暴露相关，潜伏期长达40至50年。患者通常在疾病晚期才出现临床症状，预后生存期不足12个月。尽管发达国家已禁止石棉使用，但欧洲地区的MPM发病率仍在上升，且预计全球发展中国家的发病率也将持续增长。目前学界在解析MPM的肿瘤生物学特性方面已取得显著进展，但在MPM的发病机制与肿瘤演化领域，仍存在诸多亟待解决的重要科学问题。近期针对良性组织的基因组与表观基因组测序技术进展，可为揭示MPM的早期发病阶段提供重要视角，并助力构建肿瘤演化的全景图谱。本研究提出假说：MPM是数十年间胸膜细胞损伤与再生循环的结果，随时间推移逐渐积累基因组与表观基因组层面的遗传改变。对石棉暴露人群的正常胸膜组织、早期胸膜增厚灶、胸膜斑以及MPM组织开展全基因组测序、RNA测序以及ATAC测序（Assay for Transposase-Accessible Chromatin using sequencing），将为解析这一过程提供关键依据，进而为MPM未来的诊断与治疗技术研发提供指导。