Approximately 15% of individuals affected by coronavirus disease 2019 (COVID-19) develop severe disease, and 5% to 6% are critically ill (respiratory failure and/or multiple organ dysfunction or failure). 1,2 Severely ill and critically ill patients have a high mortality rate, especially with older age and coexisting medical conditions. Because there are still insufficient data on cause of death, we describe postmortem examinations in a case series of patients with COVID-19. Methods | Between April 4 and April 19, 2020, we conducted serial postmortem examinations in patients with proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who died at the University Medical Center Augsburg (Germany). Autopsies were conducted according to published best practice. 3 Specimens from lung, heart, liver, spleen, kidney, brain, pleural effusion, and cerebrospinal fluid (CSF) were assessed. Postmortem nasopharyngeal, tracheal, bronchial swabs, pleural effusion, and CSF were tested for SARS-CoV-2 by reverse transcriptase-polymerase chain reaction. This study was approved by the local institutional review board, and written informed consent was obtained from next of kin.

Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with "classical" (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in 11 tumors diagnosed at young age, and pursued comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of > 10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity of a characteristic "androgen-type" pathomechanism in EO-PCA.

Malignancies are characterized by extensive global reprogramming of epigenetic patterns, including gains or losses in DNA methylation and changes to histone marks. Furthermore, high-resolution genome-sequencing efforts have discovered a wealth of mutations in genes encoding epigenetic regulators that have roles as 'writers', 'readers' or 'editors' of DNA methylation and/or chromatin states. In this Review, we discuss how these mutations have the potential to deregulate hundreds of targeted genes genome wide. Elucidating these networks of epigenetic factors will provide mechanistic understanding of the interplay between genetic and epigenetic alterations, and will inform novel therapeutic strategies.