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| Home > Publications database > Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element. > print |
| 001 | 169291 | ||
| 005 | 20240916115152.0 | ||
| 024 | 7 | _ | |a 10.1016/j.ajhg.2021.05.013 |2 doi |
| 024 | 7 | _ | |a pmid:34146516 |2 pmid |
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| 024 | 7 | _ | |a 1537-6605 |2 ISSN |
| 024 | 7 | _ | |a altmetric:107850235 |2 altmetric |
| 037 | _ | _ | |a DKFZ-2021-01388 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 570 |
| 100 | 1 | _ | |a Baxter, Joseph S |b 0 |
| 245 | _ | _ | |a Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element. |
| 260 | _ | _ | |a New York, NY |c 2021 |b Elsevier |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1726480282_16365 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a 2021 Jul 1;108(7):1190-1203 |
| 520 | _ | _ | |a A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 × 10-31). |
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| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, , Journals: inrepo01.inet.dkfz-heidelberg.de |
| 650 | _ | 7 | |a breast cancer risk |2 Other |
| 650 | _ | 7 | |a functional annotation |2 Other |
| 650 | _ | 7 | |a risk locus |2 Other |
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