Significance: Follicular lymphoma (FL) is a disease characterized by multiple relapses that are linked by a common progenitor bearing only a subset of the mutations found within the tumor that presents clinically. Inability to cure this disease may therefore be linked to the failure of current therapies to clear these early tumor-propagating clones. Here we further define the genetic hallmarks of this disease and model the steps in evolution through phylogenetic analysis of serial tumor biopsies. This identified CREBBP mutations as early events in genome evolution that are enriched within tumor cell progenitors and provided evidence that these mutations act by allowing immune evasion. This highlights CREBBP mutations as an attractive therapeutic target in FL and provides insight into their pathogenic mechanism.
Key Points: DLBCL can be detected in the blood by immunoglobulin high-throughput sequencing (Ig-HTS) with high specificity. Although DLBCL can be detected in leukocytes or plasma by Ig-HTS, plasma has greater sensitivity and more accurately reflects disease.
Key Points: Analysis of coding genomes of FL tumor subpopulations reveals striking clonal diversity at diagnosis and progression. Within a hierarchy of somatic evolution of FL coding genomes, many recurrent mutations are subclonal at diagnosis.
25 June 2020 in American Journal of Neuroradiology
BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) is an active worldwide pandemic with diverse complications. Stroke as a presentation has not been strongly associated with COVID-19. The authors aimed to retrospectively review a link between COVID-19 and acute stroke. MATERIALS AND METHODS: We conducted a retrospective case-control study of 41 cases and 82 control subjects matched by age, sex, and risk factors. Cases were patients who underwent stroke alert imaging with confirmed acute stroke on imaging between March 16 and April 5, 2020, at 6 hospitals across New York City. Control subjects were those who underwent stroke alertimaging during the same timeframe without imaging evidence of acute infarction. Data pertaining to diagnosis of COVID-19 infection, patient demographics, and risk factors were collected. A univariate analysis was performed to assess the covariate effect of risk factors and COVID-19 status on stroke imaging with positive findings. RESULTS: The mean age for cases and controls was 65.5 ± 15.3 years and 68.8 ± 13.2 years, respectively. Of patients with acute ischemic stroke, 46.3% had COVID-19 infection compared with 18.3% of controls (P = .001). After adjusting for age, sex, and risk factors, COVID-19 infection had a significant independent association with acute ischemic stroke compared with control subjects (OR, 3.9; 95% CI, 1.7–8.9; P = .001). CONCLUSIONS: We demonstrated that COVID-19 infection is significantly associated with imaging confirmation of acute ischemic stroke, and patients with COVID-19 should undergo more aggressive monitoring for stroke.