RNA Sequencing of Primary Cutaneous and Breast-Implant Associated Anaplastic Large Cell Lymphomas Reveals Infrequent Fusion Transcripts and Upregulation of PI3K/AKT Signaling via Neurotrophin Pathway Genes

Cutaneous and breast implant-associated anaplastic large-cell lymphomas (cALCLs and BI-ALCLs) are two localized forms of peripheral T-cell lymphomas (PTCLs) that are recognized as distinct entities within the family of ALCL. JAK-STAT signaling is a common feature of all ALCL subtypes, whereas DUSP22/IRF4, TP63 and TYK gene rearrangements have been reported in a proportion of ALK-negative sALCLs and cALCLs. Both cALCLs and BI-ALCLs differ in their gene expression profiles compared to PTCLs; however, a direct comparison of the genomic alterations and transcriptomes of these two entities is lacking. By performing RNA sequencing of 1385 genes (TruSight RNA Pan-Cancer, Illumina) in 12 cALCLs, 10 BI-ALCLs and two anaplastic lymphoma kinase (ALK)-positive sALCLs, we identified the previously reported TYK2-NPM1 fusion in 1 cALCL (1/12, 8%), and four new intrachromosomal gene fusions in 2 BI-ALCLs (2/10, 20%) involving genes on chromosome 1 (EPS15-GNG12 and ARNT-GOLPH3L) and on chromosome 17 (MYO18A-GIT1 and NF1-GOSR1). One of the two BI-ALCL samples showed a complex karyotype, raising the possibility that genomic instability may be responsible for intra-chromosomal fusions in BI-ALCL. Moreover, transcriptional analysis revealed similar upregulation of the PI3K/Akt pathway, associated with enrichment in the expression of neurotrophin signaling genes, which was more conspicuous in BI-ALCL, as well as differences, i.e., over-expression of genes involved in the RNA polymerase II transcription program in BI-ALCL and of the RNA splicing/processing program in cALCL

Predictors of poor prognosis in healthy, young, individuals with SARS-CoV-2 infections.

To identify predictors of poor prognosis in previously healthy young individuals admitted to hospital with coronavirus disease 2019 (COVID-19). We studied a cohort of patients hospitalized with COVID-19. All patients without co-morbidities, without usual treatments and ≤65 years old were selected from an international registry (HOPE-COVID-19, NCT04334291). We focused on baseline variables-symptoms and signs at admission-to analyse risk factors for poor prognosis. The primary end point was a composite of major adverse clinical events during hospitalization including mortality, mechanical ventilation, high-flow nasal oxygen therapy, prone, sepsis, systemic inflammatory response syndrome and embolic events. Overall, 773 healthy young patients were included. The primary composite end point was observed in 29% (225/773) and the overall mortality rate was 3.6% (28/773). In the combined event group, 75% (168/225) of patients were men and the mean age was 49 (±11) years, whereas in the non-combined event group, the prevalence of male gender was 43% (238/548) and the mean age was 42 (±13) years (p  Major adverse clinical events were unexpectedly high considering the baseline characteristics of the cohort. Signs of respiratory compromise at admission and male gender, were predictive for poor prognosis among young healthy patients hospitalized with COVID-19