Whole exome sequencing of a single osteosarcoma case—integrative analysis with whole transcriptome RNA-seq data

Background Osteosarcoma (OS) is a prevalent primary malignant bone tumour with unknown etiology. These highly metastasizing tumours are among the most frequent causes of cancer-related deaths. Thus, there is an urgent need for different markers, and with our study, we were aiming towards finding novel biomarkers for OS. Methods For that, we analysed the whole exome of the tumorous and non-tumour bone tissue from the same patient with OS applying next-generation sequencing. For data analysis, we used several softwares and combined the exome data with RNA-seq data from our previous study. Results In the tumour exome, we found wide genomic rearrangements, which should qualify as chromotripsis—we detected almost 3,000 somatic single nucleotide variants (SNVs) and small indels and more than 2,000 copy number variants (CNVs) in different chromosomes. Furthermore, the somatic changes seem to be associated to bone tumours, whereas germline mutations to cancer in general. We confirmed the previous findings that the most significant pathway involved in OS pathogenesis is probably the WNT/β-catenin signalling pathway. Also, the IGF1/IGF2 and IGF1R homodimer signalling and TP53 (including downstream tumour suppressor gene EI24) pathways may have a role. Additionally, the mucin family genes, especially MUC4 and cell cycle controlling gene CDC27 may be considered as potential biomarkers for OS. Conclusions The genes, in which the mutations were detected, may be considered as targets for finding biomarkers for OS. As the study is based on a single case and only DNA and RNA analysis, further confirmative studies are required

Author Correction: The genetic legacy of continental scale admixture in Indian Austroasiatic speakers

This Article contains errors in the Methods section, under subsection ‘Samples collection and genotyping’

JMJD6 is a tumorigenic factor and therapeutic target in neuroblastoma

Chromosome 17q21-ter is commonly gained in neuroblastoma, but it is unclear which gene in the region is important for tumorigenesis. The JMJD6 gene at 17q21-ter activates gene transcription. Here we show that JMJD6 forms protein complexes with N-Myc and BRD4, and is important for E2F2, N-Myc and c-Myc transcription. Knocking down JMJD6 reduces neuroblastoma cell proliferation and survival in vitro and tumor progression in mice, and high levels of JMJD6 expression in human neuroblastoma tissues independently predict poor patient prognosis. In addition, JMJD6 gene is associated with transcriptional super-enhancers. Combination therapy with the CDK7/super-enhancer inhibitor THZ1 and the histone deacetylase inhibitor panobinostat synergistically reduces JMJD6, E2F2, N-Myc, c-Myc expression, induces apoptosis in vitro and leads to neuroblastoma tumor regression in mice, which are significantly reversed by forced JMJD6 over-expression. Our findings therefore identify JMJD6 as a neuroblastoma tumorigenesis factor, and the combination therapy as a treatment strategy

Recognition of the Phanerozoic “Young Granite Gneiss” in the central Yeongnam Massif

Up to now, all the high-grade gneisses of the Korean peninsula have been regarded as Precambrian basement rocks and presence of the Phanerozoic high-grade metamorphic rocks have remained unknown. However, such granite gneiss is discovered through this study from the central Yeongnam massif near Gimcheon. SHRIMP zircon U-Pb age determinations on the granite gneiss, having well-developed gneissic foliations and migmatitic textures, reveal concordant age of ca. 250 Ma indicating the Early Triassic emplacement of this pluton, which is in contradict to the previous belief that it is a Precambrian product. Even though the granite gneiss reveals well-developed gneissic foliations and some zircons show rather low Th/U ratios, the metamorphic age has not been determined successfully. However, the age of metamorphism can be constrained as middle Triassic considering the absence of any evidences of metamorphism from the nearby granitic plutons having emplacement ages of ca. 225 Ma. Early Triassic emplacement and subsequent Middle Triassic metamorphism of the granite gneiss from the Yeongnam massif bear a remarkable resemblance to the case of South China block. We suggest the possibility that Early to Middle Triassic metamorphism of the Korean peninsula might be products of the intracontinental collisional events not directly related with the Early Triassic continental collision event

Magnetic properties of Cu nanoclusters embedded in ZnO thin films

10.1109/TMAG.2011.2145364IEEE Transactions on Magnetics47104003-4006IEMG

Intrinsic reactivation of human endogenous retroviruses in the osteosarcoma

The human genome contains human endogenous retroviruses (HERVs) and they occupy around 8% of our genome. These viruses are derived from ancient infections of retroviruses that were reverse transcribed and integrated into the genome of ancestral host animals. These viral genomes were fixed and inherited for tens of millions of years ago. Almost all of the HERVs have lost their infectivity and no known HERV is presently. The role of HERVs has been shown in the different inflammatory diseases and cancers. The goal of present study was to analyse the genome-wide transcriptional activity of HERVs in osteosarcoma. We performed RNA-seq analysis of 36 tumor-normal paired samples, raw sequencing data were used to identify HERV sequences and counts data as expressional activity. DESeq2 package was used for statistical analysis. We found massive and activation of HERVs in the osteosarcoma sample. More precisely, 58 different repeat element were differently described between normal and tumor bone with the FDR levele below 0.05. The most significantly upregulated elements were satellite elements ALR, ALR/ALPHA, ALR2, ALR6 and ALRA SAT elements. In addition, over-expression of the pericentromeric human satellite II (HSATII) and the ancient mariner transposon (HSMAR1) was found. The most down-regulated elements were HERVK22I, LTR40A, LTR40B, LTR40C and MER87B. Up-regulation of the satellite elements during cancer has been described in some previous studies. However, genome-wide analysis of all repetitive elements in the human genome is novel approach and could give additional information about the oncogenesis

Effects of Leucaena condensed tannins of differing molecular weights on in vitro CH 4 production

Condensed tannins (CT) exhibit nutritional, environmental and veterinary benefits in ruminant production. It is known that effects of CT on animal nutrition is multi-factorial, but their molecular weight (MW) and/or chemical structures play a key role in their biological activity. The average MW of five CT fractions obtained from Leucaena hybrid-Bahru (LLB) was determined using mass quadrupole time-of-flight liquid chromatography/mass spectrometry. CT within each fraction had varying degrees of polymerization with up to hexamers and molecular weights of 1348.80Da identified in the first fraction, and 494.56Da in the fifth fraction. Results show that CT fractions with the highest MW had in the highest inhibition of CH 4 production, being 62 lower than the control. In addition, the amount of CH 4 as a proportion of total gas also decreased with CT compared to control, suggesting a direct effect of CT on CH 4 production with those of higher MW exhibiting anti-methanogenic activity