Citations

Marrow adipocytes reprogrammed by myeloma cells induce bone lesions.

AimsIn thymic carcinomas, focal clear cell change is a frequent finding. In addition to a prominent, diffuse clear cell morphology, some of these carcinomas show an exuberant hyalinised extracellular matrix, and therefore probably represent a separate entity. However, a characteristic genomic alteration remains elusive. We hypothesised that, analogous to hyalinising clear cell carcinomas of the salivary gland, hyalinising clear cell carcinomas of the thymus might also harbour EWSR1 translocations.Methods and resultsWe identified nine archived cases of thymic carcinoma with focal clear cell features and two cases that showed remarkable hyalinised stroma and prominent, diffuse clear cell morphology. These two cases expressed p40 and were negative for Pax8, CD5, and CD117. Programmed death‐ligand 1 was highly positive in one case (70%), and negative in the other one. EWSR1 translocation was identified in both cases of hyalinising clear cell carcinoma, and was absent in all nine carcinomas that showed clear cell features without substantial hyalinisation. In one of the EWSR1‐translocated cases, a fusion between exon 13 and exon 6 of EWSR1 and ATF1, respectively was identified by next‐generation sequencing.ConclusionsThese findings suggest that the EWSR1 translocation and possibly the EWSR1–ATF1 fusion might be unifying genomic alterations for thymic clear cell carcinomas with prominent hyalinised stroma, for which we propose the term ‘hyalinising clear cell carcinoma of the thymus’. Because the immunophenotype is unspecific, testing for the EWSR1 translocation might be helpful in discriminating this entity from other thymic neoplasms or metastases, in particular those with clear cell change.

Suppression of ZEB1 through miR-200 expression or HDAC inhibition with mocetinostat sensitizes resistant KRAS mutant lung cancers to MEK inhibition.

How dipeptide repeats cause pathology A repeat expansion in the chromosome 9 open reading frame 72 ( C9orf72 ) gene is the most common known cause of two neurodegenerative diseases: frontotemporal dementia and amyotrophic lateral sclerosis. This expansion leads to the abnormal production of proteins of repeating dipeptides, but their contribution to disease pathogenesis remains unclear. Zhang et al. engineered a mouse model to study the consequences of one of these dipeptides—prolinearginine dipeptide repeat protein, poly(PR)—in the brain. They found that poly(PR) caused neuron loss as well as motor and memory impairments. These detrimental effects resulted from poly(PR)-induced perturbation of heterochromatin function, a tightly packed form of DNA that represses gene expression. Science , this issue p. eaav2606

AbstractIn the forensic field, ancestry‐informative markers (AIMs) showing remarkable allele frequency discrepancies can be useful in deducing the likely ancestral origin of a person or estimating the ancestry component proportions of an admixed population or individual. Diallelic single nucleotide polymorphisms are genetic markers commonly used for ancestry inference, but the genotyping methods of single nucleotide polymorphisms fail to fulfil the demands of cost‐effectiveness and simplicity of experimental manipulation. To overcome the limitations, a 39 ancestry‐informative insertion/deletion polymorphism multiplex panel was developed in the present study to perform ancestry assignment of individuals from three distinct biogeographic regions (Africa, Europe, East Asia). And in the panel design, we also attempted to incorporate AIM‐insertion/deletion polymorphisms exhibiting allelic frequency differences in Han, Uyghur, and Tibetan populations into the multiplex assay, further expecting to provide valuable information for refining ancestry inference within Chinese populations. Statistical analyses were performed to estimate efficiency of this panel in clustering individuals from three continents mentioned above into their corresponding populations, which indicated the potential of the panel in ancestry inference. Besides, we also estimated the ancestral component proportions of Uyghur group and STRUCTURE analysis revealed that Uyghurs from Urumchi city of northern Xinjiang exhibited a distinctly admixed pattern of East Asian and European ancestry components with a ratio of 49:44, reflecting the relatively higher East Asian ancestry component contribution in the gene pool of the Uyghur group.

PurposeBiomechanical properties can be used as biomarkers to diagnose tumors, monitor tumor development, and evaluate treatment efficacy. The purpose of this preliminary study is to characterize the biomechanical environment of two typical liver tumors, hemangiomas (HEMs) and hepatocellular carcinomas (HCCs), and to investigate the potential of using strain metrics as biomarkers for tumor diagnosis, based on a limited clinical dataset.MethodsMagnetic resonance (MR) tagging was used to quantify the motion and deformation of the two types of liver tumors. Displacements of the tumors arising from a heartbeat were measured over one cardiac cycle. Local biomechanical conditions of the tumors were characterized by estimating two principal strains (ε1 and ε2) and an octahedral shear strain (εsoct) of the tumor and its peripheral region. Biomechanical conditions of the tumors were compared with those of the arbitrarily selected regions from healthy volunteers.ResultsWe observed that the HCCs had significantly smaller strain values compared to their peripheral tissues. However, the HEMs did not have significantly different strains from those of the peripheral tissues, and were similar to healthy liver regions. The sensitivity of using ε1, ε2, and εsoct to diagnose HCC were all 1, while the sensitivity of using ε1, ε2, and εsoct to diagnose HEM were 0.67, 0.17, and 0.67, respectively.ConclusionsLagrangian strain metrics provide insight into the biomechanical conditions of certain liver tumors in the human body and may provide another perspective for tumor characterization and diagnosis.