GSE148277 Estrogen receptor alpha mutations in breast cancer cells cause gene expression changes through constant activity and through secondary effects ChIP-seq
Contributors : Spencer Arnesen ; Jason GertzSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensWhile breast cancer patients with tumors that express estrogen receptor α (ER) generally respond well to hormone therapies that block ER’s actions, a significant number relapse. Approximately 30% of these recurrences harbor activating mutations in ER’s ligand binding domain. ER mutations have been shown to confer ligand-independent function to ER; however, much is still unclear regarding the effect of mutant ER beyond its estrogen independence. To investigate mutant ER’s molecular effects, we developed multiple isogenic ER mutant cell lines for the two most common ER ligand binding domain mutations, Y537S and D538G. We found that these mutations induce diff erential expression of thousands of genes, the majority of which are specific to one or the other mutation and are not observed upon estrogen treatment of wildtype cells. The mutant-specific genes show consistent differential expression across ER mutant lines developed in other laboratories. The obs erved gene expression changes cannot be explained by constitutive ER activity alone, as wildtype cells with long term estrogen exposure only exhibit some of these transcriptional changes, suggesting that mutant ER causes novel regulatory effects that are not simply due to constant activity. While ER mutations have minor effects on ER genomic binding, with the ex...
Conclusions: Our report is the first study to examine the distant metastatic breast cancer proteome using FFPE tissues. The depth of our dataset allowed us to discover a novel biomarker candidate and a proteomic characteristics of distant metastatic breast cancer. Distinct molecular features of various breast cancer subtypes were also established. Our proteomic data constitute a valuable resource for research on distant metastatic breast cancer. PMID: 32489334 [PubMed]
Conclusions: In the present study, the availability of Oncotype dx testing was observed to influence the choice of chemotherapy type in the setting of early-stage bca. PMID: 32489257 [PubMed - in process]
Conclusions: Delay to the initiation of adjuvant rt after breast-conserving surgery is associated with inferior bca survival outcomes. The good prognosis for patients with early-stage bca limits the statistical power to detect an effect of delay to rt. Given that there is no plausible advantage to delay, we agree with Mackillop that time to initiation of rt should be kept "as short as reasonably achievable." PMID: 32489271 [PubMed - in process]
Conclusions: In the present study, the most recent and largest administrative database analysis of a Canadian population to date, we observed a subtype distribution consistent with previously reported data, together with comparable annual incidence and overall survival patterns. PMID: 32489268 [PubMed - in process]
Conclusions: In Ontario, the detection rate of CDH1 pvs in patients with dgc was low: no pvs were identified in patients with isolated dgc at less than 40 years of age, and 1 was identified in a patient with isolated dgc at less than 50 years of age. Isolated lbc with no dgc was observed in CDH1-positive families, as were pathology-confirmed nondgc or non-lbc malignancies, which had not previously been reported. Given a phenotype that overlaps with other hereditary conditions, multi-gene panels are recommended for all patients with dgc at less than 50 years of age and for those meeting igclc criteria. PMID: 32489267 [PubMed - in process]
Authors: Arnaout A, Varela NP, Allarakhia M, Grimard L, Hey A, Lau J, Thain L, Eisen A Abstract Background: In Ontario, there is no clearly defined standard of care for staging for distant metastasis in women with newly diagnosed and biopsy-confirmed breast cancer whose clinical presentation is suggestive of early-stage disease. This guideline addresses baseline imaging investigations for women with newly diagnosed primary breast cancer who are otherwise asymptomatic for distant metastasis. Methods: The medline and embase databases were systematically searched for evidence from January 2000 to April 2019, and t...
Publication date: Available online 3 June 2020Source: Computational and Structural Biotechnology JournalAuthor(s): Jocelyn Gal, Caroline Bailleux, David Chardin, Thierry Pourcher, Julia Gilhodes, Lun Jing, Jean-Marie Guigonis, Jean-Marc Ferrero, Gerard Milano, Baharia Mograbi, Patrick Brest, Yann Chateau, Olivier Humbert, Emmanuel Chamorey
This study is designed to determine level changes in total antioxidant status and markers of lipid peroxidation melondialdehyde (MDA) and angiogenesis vascular endothelial growth factor (VEGF) along with related micronutrients of copper, zinc, magnesium, and iron in malignant and benign breast disease tissue extracts. We assess specificity and sensitivity of those markers using the area under the curve of receiver operator characteristic (ROC) curve analysis. Association studies are done with correlation analysis. The tissue extract level of MDA markers is found to be significantly higher (14.118 ± 1.47 nmol/g tissue; p
In conclusion, we designed specific and sensitive methods to detect LALBA transcripts. We show for the first time a differential expression of these transcripts, but we need to confirm their potential use as markers in breast cancer. PMID: 32464003 [PubMed - indexed for MEDLINE]
In conclusion, PTZ was hypothesized to act effectively on mitochondria of HepG2 cells; hence it should proceed into detailed drug targeting mechanism research. PMID: 32464002 [PubMed - indexed for MEDLINE]