Approximately half of the world's 500,000 new oesophageal squamous-cell carcinoma (ESCC) cases each year occur in China. Here, we show whole-genome sequencing of DNA and RNA in 94 Chinese individuals with ESCC. We identify six mutational signatures (E1–E6), and Signature E4 is unique in ESCC linked to alcohol intake and genetic variants in alcohol-metabolizing enzymes. We discover significantly recurrent mutations in 20 protein-coding genes, 4 long non-coding RNAs and 10 untranslational regions. Functional analyses show six genes that have recurrent copy-number variants in three squamous-cell carcinomas (oesophageal, head and neck and lung) significantly promote cancer cell proliferation, migration and invasion. The most frequently affected genes by structural variation are LRP1B and TTC28. The aberrant cell cycle and PI3K-AKT pathways seem critical in ESCC. These results establish a comprehensive genomic landscape of ESCC and provide potential targets for precision treatment and prevention of the cancer.
There has been a dramatic increase in the detection of lung nodules, many of which are preneoplasia atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) or invasive adenocarcinoma (ADC). The molecular landscape and the evolutionary trajectory of lung preneoplasia have not been well defined. Here, we perform multi-region exome sequencing of 116 resected lung nodules including AAH (n = 22), AIS (n = 27), MIA (n = 54) and synchronous ADC (n = 13). Comparing AAH to AIS, MIA and ADC, we observe progressive genomic evolution at the single nucleotide level and demarcated evolution at the chromosomal level supporting the early lung carcinogenesis model from AAH to AIS, MIA and ADC. Subclonal analyses reveal a higher proportion of clonal mutations in AIS/MIA/ADC than AAH suggesting neoplastic transformation of lung preneoplasia is predominantly associated with a selective sweep of unfit subclones. Analysis of multifocal pulmonary nodules from the same patients reveal evidence of convergent evolution.
In recent years, organic–inorganic hybrid halide perovskites have attracted great attention. In view of the toxicity of lead, lead-free perovskites have been developed in order to obtain comparable or better photovoltaic performance than MAPbI3. In this study, the structural, electronic, and optical properties of pure and mixed perovskite systems were investigated by using density functional theory calculations. The results reveal that three Pb–Sn–Ge perovskites are predicted to preserve improved structural stabilities over MAPbI3. The band gaps of hybrid perovskites can be tuned by means of Sn–Ge doping. The band gap of MAPb0.50Sn0.25Ge0.25I3 is in the optimum range of 1.3–1.4 eV. Optical property analysis implies that MAPb0.50Sn0.25Ge0.25I3 possesses a comparable absorption ability in the visible light region compared with the MAPbI3 structure. In addition, the results indicate that MAPb0.50Sn0.25Ge0.25I3 with the highest power conversion efficieny of 23.65% can be chosen as a potential candidate for the light absorption layer. The amount of lead will decline to a certain extent because of the partial substitution of Pb by Sn and Ge. These results are expected to be helpful for further experiments to find new kinds of possible lead-less or lead-free perovskite materials.
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