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| Open AccessIntegrated genomic analyses of de novo pathways underlying atypical meningiomas
Meningiomas are mostly benign brain tumours with the potential for becoming atypical or malignant. Here, the authors show that primary atypical meningiomas are epigenetically and genetically distinct from benign and progressed tumours, highlighting possible therapeutic targets such as PRC2.
- Akdes Serin Harmancı
- , Mark W. Youngblood
- & Murat Günel
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Article
| Open AccessATR inhibitors as a synthetic lethal therapy for tumours deficient in ARID1A
Mutations in the BAF SWI/SNF complex subunits are frequent in cancers but selective therapeutic approaches are not available yet. Here, the authors demonstrate that defects ofARID1Aand other subunits sensitizes cancer cells to the DNA checkpoint kinase inhibitor ATR in a synthetic lethal manner.
- Chris T. Williamson
- , Rowan Miller
- & Christopher J. Lord
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Article
| Open AccessMEK inhibitors block growth of lung tumours with mutations in ataxia–telangiectasia mutated
ATM is a tumor suppressor often mutated in lung adenocarcinoma. In this study, the authors starting from a synthetic lethal screen, demonstrate that tumor cells with mutations in ATM exhibit increased sensitivity to MEK1/2 inhibition through the modulation of the AKT/mTOR pathway.
- Michal Smida
- , Ferran Fece de la Cruz
- & Sebastian M. B. Nijman
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Article
| Open AccessTumour-initiating cell-specific miR-1246 and miR-1290 expression converge to promote non-small cell lung cancer progression
miRNAs can function either as proto-oncogenes or tumour suppressors in several cancers; however their function in tumour initiating cells is unclear. Here, Zhang et al. show that tumour initiating cell-specific miR-1246 and miR-1290 promote lung cancer initiation and metastasis and could serve as prognostic markers.
- Wen Cai Zhang
- , Tan Min Chin
- & Bing Lim
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Article
| Open AccessLRF maintains genome integrity by regulating the non-homologous end joining pathway of DNA repair
Leukemia/lymphoma-related factor (LRF), a transcriptional repressor, plays key roles in cell fate decision and tumorigenesis. Here, Liu et al. show that LRF loss results in defective classical non-homologous end joining, genomic instability and hypersensitivity to ionizing radiation, revealing a transcription-independent regulation of DNA-PK complex.
- Xue-Song Liu
- , Gurushankar Chandramouly
- & Pier Paolo Pandolfi
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Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients
Somatic mutations have been reported in pancreatic adenocarcinomas. Here, Sausen et al. identify further mutations and find that mutations in the chromatin modifying gene, MLL, are associated with increased survival, and that the presence of circulating tumour DNA in the serum of patients is associated with poor survival.
- Mark Sausen
- , Jillian Phallen
- & Victor E. Velculescu
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Article
| Open AccessSingle-band upconversion nanoprobes for multiplexed simultaneous in situ molecular mapping of cancer biomarkers
The excitation–emission profiles of upconversion nanoparticles (UCNPs) make them attractive biological probes. Here the authors present a lanthanide UCNP for the in situmultiplexed detection of cancer biomarkers, with different single-colour upconversion emissions.
- Lei Zhou
- , Rui Wang
- & Fan Zhang
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Elevated oncofoetal miR-17-5p expression regulates colorectal cancer progression by repressing its target gene P130
Tumorigenesis has been likened to a form of cellular reversion to the embryonic state. Ma et al.identify a foetal miRNA as an oncogenic activator of the Wnt/β-catenin pathway in colorectal cancer, whose expression is negatively correlated with survival but is positively correlated with response to adjuvant chemotherapy.
- Yanlei Ma
- , Peng Zhang
- & Huanlong Qin
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Plasmonic substrates for multiplexed protein microarrays with femtomolar sensitivity and broad dynamic range
Protein microarrays are useful both in basic research and also in disease monitoring and diagnosis, but their dynamic range is limited. By using plasmonic gold substrates with near-infrared fluorescent enhancement, Tabakman et al. demonstrate a multiplexed protein array with improved detection limits and dynamic range.
- Scott M. Tabakman
- , Lana Lau
- & Hongjie Dai
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Identification of the PGRMC1 protein complex as the putative sigma-2 receptor binding site
The sigma-2 receptor is used as a biomarker for tumour cell proliferation but its identity is unknown. Using a novel radiolabelled probe, the authors identify progesterone receptor membrane component 1, which is overexpressed in several tumour types, as the putative sigma-2 receptor.
- Jinbin Xu
- , Chenbo Zeng
- & Robert H. Mach