Landscape of G-quadruplex DNA structural regions in breast cancer
| العنوان: | Landscape of G-quadruplex DNA structural regions in breast cancer |
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| المؤلفون: | Giovanni Marsico, Santosh Adhikari, Oscar M. Rueda, Xiaoyun Zhang, Alejandra Bruna, Carlos Caldas, David Tannahill, Alistair Martin, Katherine G. Zyner, Shankar Balasubramanian, Robert Hänsel-Hertsch, Winnie W. I. Hui, Angela Simeone, Abigail Shea |
| المصدر: | Nature Genetics. 52:878-883 |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Regulation of gene expression, 0303 health sciences, Somatic cell, Promoter, Biology, medicine.disease, G-quadruplex, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Breast cancer, chemistry, Genetics, medicine, Cancer research, Gene, Transcription factor, 030217 neurology & neurosurgery, DNA, 030304 developmental biology |
| الوصف: | Response and resistance to anticancer therapies vary due to intertumor and intratumor heterogeneity1. Here, we map differentially enriched G-quadruplex (G4) DNA structure-forming regions (∆G4Rs) in 22 breast cancer patient-derived tumor xenograft (PDTX) models. ∆G4Rs are associated with the promoters of highly amplified genes showing high expression, and with somatic single-nucleotide variants. Differences in ΔG4R landscapes reveal seven transcription factor programs across PDTXs. ∆G4R abundance and locations stratify PDTXs into at least three G4-based subtypes. ∆G4Rs in most PDTXs (14 of 22) were found to associate with more than one breast cancer subtype, which we also call an integrative cluster (IC)2. This suggests the frequent coexistence of multiple breast cancer states within a PDTX model, the majority of which display aggressive triple-negative IC10 gene activity. Short-term cultures of PDTX models with increased ∆G4R levels are more sensitive to small molecules targeting G4 DNA. Thus, G4 landscapes reveal additional IC-related intratumor heterogeneity in PDTX biopsies, improving breast cancer stratification and potentially identifying new treatment strategies. |
| تدمد: | 1546-1718 1061-4036 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::4812fbb9aa4b81a1207231bc52ec62caTest https://doi.org/10.1038/s41588-020-0672-8Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi...........4812fbb9aa4b81a1207231bc52ec62ca |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15461718 10614036 |
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