We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. We performed molecular clustering using data on chromosome-arm-level aneuploidy, DNA hypermethylation, mRNA, and miRNA expression levels and reverse-phase protein arrays, of which all, except for aneuploidy, revealed clustering primarily organized by histology, tissue type, or anatomic origin. The influence of cell type was evident in DNA-methylation-based clustering, even after excluding sites with known preexisting tissue-type-specific methylation. Integrative clustering further emphasized the dominant role of cell-of-origin patterns. Molecular similarities among histologically or anatomically related cancer types provide a basis for focused pan-cancer analyses, such as pan-gastrointestinal, pan-gynecological, pan-kidney, and pan-squamous cancers, and those related by stemness features, which in turn may inform strategies for future therapeutic development.
A novel and simple method for preparing highly photoactive nanocrystalline F--doped
TiO2 photocatalyst with anatase and brookite phase was developed by hydrolysis of titanium
tetraisopropoxide in a mixed NH4F−H2O solution. The prepared F--doped TiO2 powders
were characterized by differential thermal analysis-thermogravimetry (DTA-TG), X-ray
diffraction (XRD), X-ray photoelectron spectroscopy (XPS), UV−vis absorption spectroscopy,
photoluminescence spectra (PL), transmission electron microscopy (TEM), and BET surface
areas. The photocatalytic activity was evaluated by the photocatalytic oxidation of acetone
in air. The results showed that the crystallinity of anatase was improved upon F- doping.
Moreover, fluoride ions not only suppressed the formation of brookite phase but also
prevented phase transition of anatase to rutile. The F--doped TiO2 samples exhibited stronger
absorption in the UV−visible range with a red shift in the band gap transition. The
photocatalytic activity of F--doped TiO2 powders prepared by this method exceeded that of
Degussa P25 when the molar ratio of NH4F to H2O was kept in the range of 0.5−3.
SUMMARY
We performed integrated genomic, transcriptomic and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1 and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1 and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine.
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