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Identification of potential regulatory mutations using multi-omics analysis and haplotyping of lung adenocarcinoma cell lines.

Identification of potential regulatory mutations using multi-omics analysis and haplotyping of lung adenocarcinoma cell lines.
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Sereewattanawoot S, Suzuki A, Seki M, Sakamoto Y, Kohno T, Sugano S, Tsuchihara K, Suzuki Y,


Sereewattanawoot S, Suzuki A, Seki M, Sakamoto Y, Kohno T, Sugano S, Tsuchihara K, Suzuki Y, (click to view)

Sereewattanawoot S, Suzuki A, Seki M, Sakamoto Y, Kohno T, Sugano S, Tsuchihara K, Suzuki Y,

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Scientific reports 2018 03 218(1) 4926 doi 10.1038/s41598-018-23342-1

Abstract

The functional relevancy of mutations occurring in the regulatory regions in cancers remains mostly elusive. Here, we identified and analyzed regulatory mutations having transcriptional consequences in lung adenocarcinoma-derived cell lines. We phased the mutations in the regulatory regions to the downstream heterozygous SNPs in the coding regions and examined whether the ChIP-Seq variant tags of the regulatory SNVs and the RNA-Seq variant tags of their target transcripts showed biased frequency between the mutant and reference alleles. We identified 137 potential regulatory mutations affecting the transcriptional regulation of 146 RefSeq transcripts with at least 84 SNVs that create and/or disrupt potential transcription factor binding sites. For example, in the regulatory region of NFATC1 gene, a novel and active binding site for the ETS transcription factor family was created. Further examination revealed that 31 of these disruptions were presented in clinical lung adenocarcinoma samples and were associated with prognosis of patients.

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