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https://hdl.handle.net/2440/99978
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Type: | Journal article |
Title: | Regulators of genetic risk of breast cancer identified by integrative network analysis |
Author: | Castro, M. De Santiago, I. Campbell, T. Vaughn, C. Hickey, T. Ross, E. Tilley, W. Markowetz, F. Ponder, B. Meyer, K. |
Citation: | Nature Genetics, 2016; 48(1):12-21 |
Publisher: | Nature Publishing Group |
Issue Date: | 2016 |
ISSN: | 1061-4036 1546-1718 |
Statement of Responsibility: | Mauro A A Castro, Ines de Santiago, Thomas M Campbell, Courtney Vaughn, Theresa E Hickey, Edith Ross, Wayne D Tilley, Florian Markowetz, Bruce A J Ponder and Kerstin B Meyer |
Abstract: | Genetic risk for breast cancer is conferred by a combination of multiple variants of small effect. To better understand how risk loci might combine, we examined whether risk-associated genes share regulatory mechanisms. We created a breast cancer gene regulatory network comprising transcription factors and groups of putative target genes (regulons) and asked whether specific regulons are enriched for genes associated with risk loci via expression quantitative trait loci (eQTLs). We identified 36 overlapping regulons that were enriched for risk loci and formed a distinct cluster within the network, suggesting shared biology. The risk transcription factors driving these regulons are frequently mutated in cancer and lie in two opposing subgroups, which relate to estrogen receptor (ER)(+) luminal A or luminal B and ER(-) basal-like cancers and to different luminal epithelial cell populations in the adult mammary gland. Our network approach provides a foundation for determining the regulatory circuits governing breast cancer, to identify targets for intervention, and is transferable to other disease settings. |
Keywords: | Breast Neoplasms |
Description: | Published online 30 November 2015 |
Rights: | © 2016 Nature America, Inc. All rights reserved. |
DOI: | 10.1038/ng.3458 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1008349 http://purl.org/au-research/grants/nhmrc/1084416 |
Published version: | http://dx.doi.org/10.1038/ng.3458 |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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