@article{689be3c59c05457b8780919ceeba7dce,
title = "Identifying DNase I hypersensitive sites as driver distal regulatory elements in breast cancer",
abstract = "Efforts to identify driver mutations in cancer have largely focused on genes, whereas non-coding sequences remain relatively unexplored. Here we develop a statistical method based on characteristics known to influence local mutation rate and a series of enrichment filters in order to identify distal regulatory elements harboring putative driver mutations in breast cancer. We identify ten DNase I hypersensitive sites that are significantly mutated in breast cancers and associated with the aberrant expression of neighboring genes. A pan-cancer analysis shows that three of these elements are significantly mutated across multiple cancer types and have mutation densities similar to protein-coding driver genes. Functional characterization of the most highly mutated DNase I hypersensitive sites in breast cancer (using in silico and experimental approaches) confirms that they are regulatory elements and affect the expression of cancer genes. Our study suggests that mutations of regulatory elements in tumors likely play an important role in cancer development.",
author = "Matteo D'antonio and Donate Weghorn and Agnieszka D'antonio-Chronowska and Florence Coulet and Olson, {Katrina M.} and Christopher Deboever and Frauke Drees and Angelo Arias and Hakan Alakus and Richardson, {Andrea L.} and Schwab, {Richard B.} and Farley, {Emma K.} and Sunyaev, {Shamil R.} and Frazer, {Kelly A.}",
note = "Funding Information: This work was supported by NIH grants UL1TR000100 and P30CA023100. Equipment in the Neuroscience Microscopy core was used for the Ciona experiments; this core is supported by the UCSD School of Medicine Microscopy Core Grant P30 NS047101. CD is supported in part by the University of California, San Diego, Genetics Training Program through an institutional training grant from the National Institute of General Medical Sciences (T32GM008666) and the California Institute for Regenerative Medicine (CIRM) Interdisciplinary Stem Cell Training Program at UCSD II (TG2-01154). HA is supported by a grant from the German Cancer Aid (#109790). We thank Kristen Jepsen, Hiroko Matsui, Aquila Fatima, Mahdieh Khosroheidari and Marika Smith for assistance. We thank Sharmeela Kaushal and Scott Vandenberg for providing breast cancer samples. We thank Richard Kolodner, Erin Smith and Olivier Harismendy for comments. Publisher Copyright: {\textcopyright} 2017 The Author(s).",
year = "2017",
month = dec,
day = "1",
doi = "10.1038/s41467-017-00100-x",
language = "English (US)",
volume = "8",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}