Anaplastic thyroid cancer (ATC) and advanced differentiated thyroid cancers (DTCs) show fatal outcomes, unlike DTCs. Here, we demonstrate mutational landscape of 27 ATCs and 86 advanced DTCs by massively-parallel DNA sequencing, and transcriptome of 13 ATCs and 12 advanced DTCs were profiled by RNA sequencing. TERT , AKT1 , PIK3CA , and EIF1AX were frequently co-mutated with driver genes ( BRAF V600E and RAS ) in advanced DTCs as well as ATC, but tumor suppressors (e.g., TP53 and CDKN2A ) were predominantly altered in ATC. CDKN2A loss was significantly associated with poor disease-specific survival in patients with ATC or advanced DTCs, and up-regulation of CD274 (PD-L1) and PDCD1LG2 (PD-L2). Transcriptome analysis revealed a fourth molecular subtype of thyroid cancer (TC), ATC-like, which hardly reflects the molecular signatures in DTC. Furthermore, the activation of JAK-STAT signaling pathway could be a potential druggable target in RAS -positive ATC. Our findings provide insights for precision medicine in patients with advanced TCs.

PD-L1 and PD-1 were expressed variably in DLBCLs by tumour cells and tumour-infiltrating immune cells and might be potential therapeutic targets using PD-1/PD-L1 blockade.

Dynamin, a high-molecular-weight GTPase, plays a critical role in vesicle formation at the plasma membrane during endocytosis in animal cells. Here we report the identification of a new dynamin homolog in Arabidopsis named Arabidopsis dynamin-like 6 (ADL6). ADL6 is quite similar to dynamin I in its structural organization: a conserved GTPase domain at the N terminus, a pleckstrin homology domain at the center, and a Pro-rich motif at the C terminus. In the cell, a majority of ADL6 is associated with membranes. Immunohistochemistry and in vivo targeting experiments revealed that ADL6 is localized to the Golgi apparatus. Expression of the dominant negative mutant ADL6[K51E] in Arabidopsis protoplasts inhibited trafficking of cargo proteins destined for the lytic vacuole and caused them to accumulate at the trans-Golgi network. In contrast, expression of ADL6[K51E] did not affect trafficking of a cargo protein, H(+)-ATPase:green fluorescent protein, destined for the plasma membrane. These results suggest that ADL6 is involved in vesicle formation for vacuolar trafficking at the trans-Golgi network but not for trafficking to the plasma membrane in plant cells.

Background:Macrophages are a component of a tumor’s microenvironment and have various roles in tumor progression and metastasis. This study evaluated the relationships between tumor-associated macrophage (TAM) density and clinical outcomes in 14 different types of human cancers.Methods:We investigated TAM density in human tissue microarray sections from 14 different types of human cancers (n = 266) and normal thyroid, lung, and breast tissues (n = 22). The five-year survival rates of each cancer were obtained from the 2011 Korea Central Cancer Registry.Results:Among 13 human cancers, excluding thyroid cancer, pancreas, lung, and gallbladder cancers had the highest density of CD163-positive macrophages (7.0±3.5%, 6.9±7.4%, and 6.9 ± 5.5%, respectively). The five-year relative survival rates of these cancers (pancreas, 8.7%; lung, 20.7%; gallbladder, 27.5%) were lower than those of other cancers. The histological subtypes in thyroid cancer exhibited significantly different CD163-positive macrophages densities (papillary, 1.8 ± 1.6% vs anaplastic, 22.9 ± 17.1%; p < .001), but no significant difference between histological subtypes was detected in lung and breast cancers. Moreover, there was no significant difference in CD163-positive macrophages densities among the TNM stages in lung, breast, and thyroid cancers.Conclusions:Cancers with higher TAM densities (pancreas, lung, anaplastic thyroid, and gallbladder) were associated with poor survival rate.