RESUMEN
Glioblastoma is characterized by widespread genetic and transcriptional heterogeneity, yet little is known about the role of the epigenome in glioblastoma disease progression. Here, we present genome-scale maps of DNA methylation in matched primary and recurring glioblastoma tumors, using data from a highly annotated clinical cohort that was selected through a national patient registry. We demonstrate the feasibility of DNA methylation mapping in a large set of routinely collected FFPE samples, and we validate bisulfite sequencing as a multipurpose assay that allowed us to infer a range of different genetic, epigenetic, and transcriptional characteristics of the profiled tumor samples. On the basis of these data, we identified subtle differences between primary and recurring tumors, links between DNA methylation and the tumor microenvironment, and an association of epigenetic tumor heterogeneity with patient survival. In summary, this study establishes an open resource for dissecting DNA methylation heterogeneity in a genetically diverse and heterogeneous cancer, and it demonstrates the feasibility of integrating epigenomics, radiology, and digital pathology for a national cohort, thereby leveraging existing samples and data collected as part of routine clinical practice.
Asunto(s)
Metilación de ADN/genética , Genoma Humano/genética , Glioblastoma/genética , Recurrencia Local de Neoplasia/genética , Mapeo Cromosómico , Progresión de la Enfermedad , Epigénesis Genética , Femenino , Heterogeneidad Genética , Glioblastoma/patología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Recurrencia Local de Neoplasia/patologíaRESUMEN
A 58-year-old man with an acute stroke suffered from splenic rupture. Streptococcus bovis was found in blood cultures, and gram-negative cocci were found in the infarcted spleen. Hemorrhagic transformation of the stroke occurred. Echocardiography showed aortic endocarditis. Cardiac surgery was not performed because of concern about cerebral bleeding. The patient died due to cerebral rehemorrhage after 3 weeks.