We propose to definitively characterise the somatic genetics of matched pair breast cancer cell lines through generation of comprehensive... Show More
We propose to definitively characterise the somatic genetics of matched pair breast cancer cell lines through generation of comprehensive catalogues of somatic mutations by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.
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This study includes 2 datasets:
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The disordered transcriptomes of cancerÂ encompass direct effects of somatic mutation on transcription; co-ordinatedÂ secondary alterations in transcriptional pathways; and increasedÂ transcriptional noise. To catalogue the rules governing how somatic mutationÂ Overall, 59% of 6980 exonicÂ substitutions wereÂ expressed. Compared to other classes, nonsense mutations showed lowerÂ expression levels than expected withÂ patterns characteristic ofÂ nonsense-mediated decay. 14% of 4234 genomic rearrangements causedÂ transcriptional abnormalities,Â including exon skips, exon reusage, fusionÂ transcripts and premature poly-adenylation. We found productive, stableÂ transcriptionÂ from sense-to-antisense gene fusions and gene-to-intergenicÂ rearrangements, suggesting that these mutation classes may drive moreÂ transcriptional disruption than previously suspected. Systematic integration ofÂ transcriptome with genome data therefore reveals theÂ rules by whichÂ transcriptional machinery interprets somatic mutation.