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10.1038/ncomms15943 http://scihub22266oqcxt.onion/10.1038/ncomms15943 C5490262!5490262 !28649990     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28649990 &cmd=llinks): Failed to open stream: HTTP request failed! 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A pan-cancer genome-wide analysis reveals tumour dependencies by induction of nonsense-mediated decay |pdf=|usr=}}{{28649990 }} gab.com Text A pan-cancer genome-wide analysis reveals tumour dependencies by induction of nonsense-mediated decay JO: Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=28649990 #FOAvip Nonsense-mediated decay (NMD) eliminates transcripts with premature termination codons. Although NMD-induced loss-of-function has been shown to contribute to the genesis of particular cancers, its global functional consequence in tumours has not been characterized. Here we develop an algorithm to predict NMD and apply it on somatic mutations reported in The Cancer Genome Atlas. We identify more than 73?K mutations that are predicted to elicit NMD (NMD-elicit). NMD-elicit mutations in tumour suppressor genes (TSGs) are associated with significant reduction in gene expression. We discover cancer-specific NMD-elicit signatures in TSGs and cancer-associated genes. Our analysis reveals a previously unrecognized dependence of hypermutated tumours on hypofunction of genes that are involved in chromatin remodelling and translation. Half of hypermutated stomach adenocarcinomas are associated with NMD-elicit mutations of the translation initiators LARP4B and EIF5B. Our results unravel strong therapeutic opportunities by targeting tumour dependencies on NMD-elicit mutations. Twit Text FOAVip A pan-cancer genome-wide analysis reveals tumour dependencies by induction of nonsense-mediated decay ????Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=28649990 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28649990 #FOAvip English Wikipedia <ref>{{Cite pmid|28649990 }}</ref> A pan-cancer genome-wide analysis reveals tumour dependencies by induction of nonsense-mediated decay #MMPMID28649990 Hu Z ; Yau C ; Ahmed AA Nat Commun 2017[Jun]; 8 (ä): 15943 PMID28649990 show ga Nonsense-mediated decay (NMD) eliminates transcripts with premature termination codons. Although NMD-induced loss-of-function has been shown to contribute to the genesis of particular cancers, its global functional consequence in tumours has not been characterized. Here we develop an algorithm to predict NMD and apply it on somatic mutations reported in The Cancer Genome Atlas. We identify more than 73?K mutations that are predicted to elicit NMD (NMD-elicit). NMD-elicit mutations in tumour suppressor genes (TSGs) are associated with significant reduction in gene expression. We discover cancer-specific NMD-elicit signatures in TSGs and cancer-associated genes. Our analysis reveals a previously unrecognized dependence of hypermutated tumours on hypofunction of genes that are involved in chromatin remodelling and translation. Half of hypermutated stomach adenocarcinomas are associated with NMD-elicit mutations of the translation initiators LARP4B and EIF5B. Our results unravel strong therapeutic opportunities by targeting tumour dependencies on NMD-elicit mutations. |*Nonsense Mediated mRNA Decay [MESH] |Algorithms [MESH] |Autoantigens/genetics/metabolism [MESH] |Cohort Studies [MESH] |Genome [MESH] |Humans [MESH] |Mutation [MESH] |Neoplasms/*genetics/metabolism [MESH] |RNA, Messenger/*genetics/metabolism [MESH] |Ribonucleoproteins/genetics/metabolism [MESH]A pan-cancer genome-wide analysis reveals tumour dependencies by induc(epmc).pdf DeepDyve Pubget Overpricing