SUMMARY Liver cancer has the second highest worldwide cancer mortality rate and has limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases by whole exome sequencing and DNA copy number analyses, and 196 HCC also by DNA methylation, RNA, miRNA, and proteomic expression. DNA sequencing and mutation analysis identified significantly mutated genes including LZTR1, EEF1A1, SF3B1, and SMARCA4. Significant alterations by mutation or down-regulation by hypermethylation in genes likely to result in HCC metabolic reprogramming (ALB, APOB, and CPS1) were observed. Integrative molecular HCC subtyping incorporating unsupervised clustering of five data platforms identified three subtypes, one of which was associated with poorer prognosis in three HCC cohorts. Integrated analyses enabled development of a p53 target gene expression signature correlating with poor survival. Potential therapeutic targets for which inhibitors exist include WNT signaling, MDM4, MET, VEGFA, MCL1, IDH1, TERT, and immune checkpoint proteins CTLA-4, PD-1, and PD-L1.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has turned into a global pandemic. No agent has proved effective against coronavirus infections, and the development of novel therapeutics is critical to solve this public health crisis. Granulocyte-macrophage colony-stimulating factor (GM-CSF), an important myelopoietic growth factor and pro-inflammatory cytokine, has attracted great interest as a therapeutic target in COVID-19. Increased percentages of GM-CSF-expressing leukocytes have been found in the blood of patients with COVID-19 (ref. 1), and inhibition of GM-CSF has shown benefit in animal studies of many hyperinflammatory conditions 2,3 that are thought to be pathologically similar to late stages of COVID-19. As of 28 May 2020, six companies had initiated randomized controlled clinical trials and open-label studies and/or expanded access/ compassionate use programmes assessing the use of monoclonal antibodies (mAbs) to GM-CSF or GM-CSF receptor (GM-CSFR) to treat various stages of COVID-19 (refs 4-9). Conversely, GM-CSF plays an important role in alveolar macrophage homeostasis and lung pathogen clearance 2 , and investigator-initiated trials are studying the administration of recombinant human GM-CSF (sargramostim) in patients with respiratory failure due to COVID-19.

Gene fusion represents a class of molecular aberrations in cancer and has been exploited for therapeutic purposes. In this paper we describe TumorFusions, a data portal that catalogues 20 731 gene fusions detected in 9966 well characterized cancer samples and 648 normal specimens from The Cancer Genome Atlas (TCGA). The portal spans 33 cancer types in TCGA. Fusion transcripts were identified via a uniform pipeline, including filtering against a list of 3838 transcript fusions detected in a panel of 648 non-neoplastic samples. Fusions were mapped to somatic DNA rearrangements identified using whole genome sequencing data from 561 cancer samples as a means of validation. We observed that 65% of transcript fusions were associated with a chromosomal alteration, which is annotated in the portal. Other features of the portal include links to SNP array-based copy number levels and mutational patterns, exon and transcript level expressions of the partner genes, and a network-based centrality score for prioritizing functional fusions. Our portal aims to be a broadly applicable and user friendly resource for cancer gene annotation and is publicly available at http://www.tumorfusions.org.

MSCs can be used as natural biofactories to produce Exo-miR124, which is an effective antiglioma agent worthy of further clinical evaluation.

These data support targeting HDACs and KDM1A in combination as a strategy for GBM and identifies TP53 and TP73 as being altered in response to treatment.