دورية أكاديمية
Genes Predisposed to DNA Hypermethylation during Acquired Resistance to Chemotherapy Are Identified in Ovarian Tumors by Bivalent Chromatin Domains at Initial Diagnosis.
| العنوان: | Genes Predisposed to DNA Hypermethylation during Acquired Resistance to Chemotherapy Are Identified in Ovarian Tumors by Bivalent Chromatin Domains at Initial Diagnosis. |
|---|---|
| المؤلفون: | Curry E; Department Surgery & Cancer, Imperial College London, London, United Kingdom., Zeller C; Department Surgery & Cancer, Imperial College London, London, United Kingdom., Masrour N; Department Surgery & Cancer, Imperial College London, London, United Kingdom., Patten DK; Department Surgery & Cancer, Imperial College London, London, United Kingdom., Gallon J; Department Surgery & Cancer, Imperial College London, London, United Kingdom., Wilhelm-Benartzi CS; Centre for Trials Research, Cardiff University, Cardiff, United Kingdom., Ghaem-Maghami S; Department Surgery & Cancer, Imperial College London, London, United Kingdom., Bowtell DD; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Brown R; Department Surgery & Cancer, Imperial College London, London, United Kingdom. b.brown@imperial.ac.uk.; Institute of Cancer Research, Sutton, United Kingdom. |
| المصدر: | Cancer research [Cancer Res] 2018 Mar 15; Vol. 78 (6), pp. 1383-1391. Date of Electronic Publication: 2018 Jan 16. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-7445 (Electronic) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Baltimore, Md. : American Association for Cancer Research Original Publication: Chicago [etc.] |
| مواضيع طبية MeSH: | Carcinoma, Ovarian Epithelial/*drug therapy , DNA Methylation/*genetics , Drug Resistance, Neoplasm/*genetics , Ovarian Neoplasms/*drug therapy, Carcinoma, Ovarian Epithelial/genetics ; Chromatin/genetics ; Chromatin Immunoprecipitation ; CpG Islands ; DNA Methylation/drug effects ; Drug Resistance, Neoplasm/drug effects ; Epigenesis, Genetic ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Silencing ; Histone Code ; Histones ; Humans ; Ovarian Neoplasms/genetics ; Promoter Regions, Genetic |
| مستخلص: | Bivalent chromatin domains containing both active H3K4me3 and repressive H3K27me3 histone marks define gene sets poised for expression or silencing in differentiating embryonic stem (ES) cells. In cancer cells, aberrantly poised genes may facilitate changes in transcriptional states after exposure to anticancer drugs. In this study, we used ChIP-seq to characterize genome-wide positioning of H3K4me3- and H3K27me3-associated chromatin in primary high-grade serous ovarian carcinomas and in normal ovarian surface and fallopian tube tissue. Gene sets with proximal bivalent marks defined in this manner were evaluated subsequently as signatures of systematic change in DNA methylation and gene expression, comparing pairs of tissue samples taken from patients at primary presentation and relapse following chemotherapy. We found that gene sets harboring bivalent chromatin domains at their promoters in tumor tissue, but not normal epithelia, overlapped with Polycomb-repressive complex target genes as well as transcriptionally silenced genes in normal ovarian and tubal stem cells. The bivalently marked genes we identified in tumors before chemotherapy displayed increased promoter CpG methylation and reduced gene expression at relapse after chemotherapy of ovarian cancer. Overall, our results support the hypothesis that preexisting histone modifications at genes in a poised chromatin state may lead to epigenetic silencing during acquired drug resistance. Significance: These results suggest epigenetic targets for intervention to prevent the emergence of cancer drug resistance. Cancer Res; 78(6); 1383-91. ©2018 AACR . (©2018 American Association for Cancer Research.) |
| معلومات مُعتمدة: | 15954 United Kingdom CRUK_ Cancer Research UK; 25350 United Kingdom CRUK_ Cancer Research UK; A13086 United Kingdom CRUK_ Cancer Research UK |
| المشرفين على المادة: | 0 (Chromatin) 0 (Histones) 0 (histone H3 trimethyl Lys4) |
| تواريخ الأحداث: | Date Created: 20180118 Date Completed: 20190520 Latest Revision: 20240210 |
| رمز التحديث: | 20240210 |
| DOI: | 10.1158/0008-5472.CAN-17-1650 |
| PMID: | 29339543 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1538-7445 |
|---|---|
| DOI: | 10.1158/0008-5472.CAN-17-1650 |