背景:肺硬化性肺细胞瘤(PSP)是一种罕见的肺肿瘤,恶性潜能低,主要影响女性。PSP的初步研究主要集中在分析使用常规X射线或CT成像发现的特征。近年来,由于下一代测序(NGS)的广泛使用,在分子水平上对PSP的研究已经出现。方法:涉及基因组学的分析方法,影像组学,并进行了病理组学。基因组学研究涉及DNA和RNA分析。DNA分析包括患者的肿瘤和种系组织,并涉及靶向组测序和拷贝数分析。RNA分析包括肿瘤和邻近的正常组织,以及涉及表达突变的研究,差异基因表达,基因融合和分子途径。将影像组学方法用于临床成像研究,将病理组学技术应用于肿瘤全载玻片图像。结果:一项全面的分子谱分析工作,涉及50多个基因组分析,对应于这种罕见的肺部肿瘤的16个测序数据集,以及详细的放射组学和病理组学分析,以揭示患者肿瘤的病因和分子行为。揭示了驱动突变(AKT1)和受损的肿瘤抑制途径(TP53)。为了确保本研究的准确性和可重复性,一种被称为NPARS的软件基础设施和方法,它封装了NGS和相关数据,开源软件库和工具,包括版本,并使用了大型复杂基因组研究的报告特征。结论:超越描述性分析,转向对肿瘤病因的更多功能理解,行为,和提高治疗的可预测性需要一系列的定量分子医学方法和整合。迄今为止,这是对PSP患者进行的最全面的研究,这是一种罕见的肺部肿瘤。详细的放射学,进行病理和基因组分子谱分析方法以揭示有关病因和分子行为的见解。如果复发,根据未发现的分子研究结果,提出了合理的治疗方案。
Background: Pulmonary Sclerosing Pneumocytoma (PSP) is a rare tumor of the lung with a low malignant potential that primarily affects females. Initial studies of PSP focused primarily on analyzing features uncovered using conventional X-ray or CT imaging. In recent years, because of the widespread use of next-generation sequencing (NGS), the study of PSP at the molecular-level has emerged. Methods: Analytical approaches involving genomics, radiomics, and
pathomics were performed. Genomics studies involved both DNA and RNA analyses. DNA analyses included the patient\'s tumor and germline tissues and involved targeted panel sequencing and copy number analyses. RNA analyses included tumor and adjacent normal tissues and involved studies covering expressed mutations, differential gene expression, gene fusions and molecular pathways. Radiomics approaches were utilized on clinical imaging studies and
pathomics techniques were applied to tumor whole slide images. Results: A comprehensive molecular profiling endeavor involving over 50 genomic analyses corresponding to 16 sequencing datasets of this rare neoplasm of the lung were generated along with detailed radiomic and pathomic analyses to reveal insights into the etiology and molecular behavior of the patient\'s tumor. Driving mutations (AKT1) and compromised tumor suppression pathways (TP53) were revealed. To ensure the accuracy and reproducibility of this study, a software infrastructure and methodology known as NPARS, which encapsulates NGS and associated data, open-source software libraries and tools including versions, and reporting features for large and complex genomic studies was used. Conclusion: Moving beyond descriptive analyses towards more functional understandings of tumor etiology, behavior, and improved therapeutic predictability requires a spectrum of quantitative molecular medicine approaches and integrations. To-date this is the most comprehensive study of a patient with PSP, which is a rare tumor of the lung. Detailed radiomic, pathomic and genomic molecular profiling approaches were performed to reveal insights regarding the etiology and molecular behavior. In the event of recurrence, a rational therapy plan is proposed based on the uncovered molecular findings.