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Somatic alterations of the genome are a leading cause of cancer development and progression.While advances in sequencing technologies have enabled the discovery of alterations in proteincoding genes in large cohorts of cancer-derived samples,genome-wide surveys of somatic alterations also revealed that a subsequent amount also cluster within non-coding regions of the genome.Unraveling the implications of somatic mutations in non-coding and intergenic regions of the genome is still a challenge.Within cell nuclei,the genome is compactly folded.Chromatin Interaction Analysis with PairedEnd Tag(ChIA-PET)has been employed to systematically analyze genome-wide chromatin folding.We hypothesize that intergenic somatic mutations arises in distant enhancer regulatory regions and are physical linked to their target genes through chromatin interactions,thus providing a mechanism by which those mutations act on gene regulation and carcinogenesis.We have developed ChIA-PETTER,a new,robust method of calling chromatin interactions and reprocessed all the published chromatin interaction libraries to-date,creating a large resource of chromatin interactions detected in breast and blood cancer derived cell lines genomes.We have combined this resource with The Cancer Genome Atlas consortium collection of genome-wide somatic mutation hotspots and identified thousands of chromatin loops between distant intergenic somatic mutation hotspots containing regions and known genes promoter regions in the model cancer cell lines K562,GM12878(leukemia)and MCF-7(breast carcinoma).To gain insights into their potential functions and mechnisms of action,we are integrating this data with both genome-wide transcription factor binding and histone modification surveys in the breast cancer cell line MCF7 and with gene expression profiles from breast cancer patients harboring the chromatin interaction associated somatic mutation hotspots.