Publications by authors named "Spencer Arnesen"
Unlabelled: Activating estrogen receptor alpha (ER; also known as ESR1) mutations are present in primary endometrial and metastatic breast cancers, promoting estrogen-independent activation of the receptor. Functional characterizations in breast cancer have established unique molecular and phenotypic consequences of the receptor, yet the impact of ER mutations in endometrial cancer has not been fully explored. In this study, we used CRISPR-Cas9 to model the clinically prevalent ER-Y537S mutation and compared results with ER-D538G to discover allele-specific differences between ER mutations in endometrial cancer.
View Article and Find Full Text PDFEstrogen receptor α (ER) mutations occur in up to 30% of metastatic ER-positive breast cancers. Recent data has shown that ER mutations impact the expression of thousands of genes not typically regulated by wildtype ER. While the majority of these altered genes can be explained by constant activity of mutant ER or genomic changes such as altered ER binding and chromatin accessibility, as much as 33% remain unexplained, indicating the potential for post-transcriptional effects.
View Article and Find Full Text PDFArticle Synopsis
- About one-third of ER+ metastatic breast cancers have mutations in the estrogen receptor α (ESR1), primarily linked to resistance to treatments.
- This study found that ESR1 mutations were present in distant recurrences of breast cancer, not in local ones, indicating a specific role for these mutations in metastasis.
- Further research showed that these mutations alter cell adhesion properties, leading to more compact circulating tumor cell (CTC) clusters in patients, suggesting that targeting these mutations could be a potential therapeutic strategy for advanced breast cancer.
While breast cancer patients with tumors that express estrogen receptor α (ER) generally respond well to hormone therapies that block ER activity, a significant number of patients relapse. Approximately 30% of these recurrences harbor activating mutations in the ligand binding domain (LBD) of ER, which have been shown to confer ligand-independent function. However, much is still unclear regarding the effect of mutant ER beyond its estrogen independence.
View Article and Find Full Text PDFArticle Synopsis
- Mutations in the estrogen receptor alpha (ER) are found in over 40% of metastatic breast cancers that resist aromatase inhibitor therapy, indicating a shift in hormone dependency among these tumors.
- Metastases with mutant ER showed different immune cell profiles and hormone receptor levels compared to those with wild-type ER, pointing to a potential mechanism of survival beyond traditional hormone reliance.
- Targeting proteins associated with mutant ER tumors, such as androgen receptor (AR) and chitinase-3-like protein 1 (CHI3L1), may enhance the effectiveness of treatments like fulvestrant and open avenues for immunotherapy in patients with these mutations.
Estrogen receptor 1 () mutations have been identified in hormone therapy-resistant breast cancer and primary endometrial cancer. Analyses in breast cancer suggest that mutant ESR1 exhibits estrogen-independent activity. In endometrial cancer, mutations are associated with worse outcomes and less obesity, however, experimental investigation of these mutations has not been performed.
View Article and Find Full Text PDFPremise Of The Study: Invasive species are often initially restricted to a narrow range and may then expand through any of multiple mechanisms including phenotypic plasticity, in situ evolution, or selection on traits preadapted for new habitats. Our study used population genetics to explore possible processes by which the highly selfing invasive annual grass has expanded into montane environments.
Methods: We used 69 single nucleotide polymorphic (SNP) markers to genotype ca.