Abstract

Breast cancer risk is strongly associated with an intergenic region on 11q13. We have previously shown that the strongest risk-associated SNPs fall within a distal enhancer that regulates CCND1. Here, we report that, in addition to regulating CCND1, this enhancer regulates two estrogen-regulated long noncoding RNAs, CUPID1 and CUPID2. We provide evidence that the risk-associated SNPs are associated with reduced chromatin looping between the enhancer and the CUPID1 and CUPID2 bidirectional promoter. We further show that CUPID1 and CUPID2 are predominantly expressed in hormone-receptor-positive breast tumors and play a role in modulating pathway choice for the repair of double-strand breaks. These data reveal a mechanism for the involvement of this region in breast cancer.

Authors	Betts, Joshua A.; Marjaneh, Mahdi Moradi; Al-Ejeh, Fares; Lim, Yi Chieh; Shi, Wei; Sivakumaran, Haran; Tropee, Romain; Patch, Ann-Marie; Clark, Michael B.; Bartonicek, Nenad; Wiegmans, Adrian P.; Hillman, Kristine M.; Kaufmann, Susanne; Bain, Amanda L.; Gloss, Brian S.; Crawford, Joanna; Kazakoff, Stephen; Wani, Shivangi; Wen, Shu W.; Day, Bryan; Moller, Andreas; Cloonan, Nicole; Pearson, John; Brown, Melissa A.; Mercer, Timothy R.; Waddell, Nicola; Khanna, Kum Kum; Dray, Eloise; Dinger, Marcel E.; Edwards, Stacey L.; French, Juliet D.
Journal	AMERICAN JOURNAL OF HUMAN GENETICS
Pages	255-266
Volume	101
Date	1/08/2017
Grant ID	1021731
Funding Body	National Health and Medical Research Council of Australia (NHMRC)
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1016/j.ajhg.2017.07.007