Endometrial tumorigenesis involves epigenetic plasticity demarcating non-coding somatic mutations and 3D-genome alterations

Background: The incidence and mortality of endometrial cancer (EC) is on the rise. Eighty-five percent of ECs depend on estrogen receptor alpha (ERα) for proliferation, but little is known about its transcriptional regulation in these tumors. Results: We generate epigenomics, transcriptomics, and Hi-C datastreams in healthy and tumor endometrial tissues, identifying robust ERα reprogramming and profound alterations in 3D genome organization that lead to a gain of tumor-specific enhancer activity during EC development. Integration with endometrial cancer risk single-nucleotide polymorphisms and whole-genome sequencing data from primary tumors and metastatic samples reveals a striking enrichment of risk variants and non-coding somatic mutations at tumor-enriched ERα sites. Through machine learning-based predictions and interaction proteomics analyses, we identify an enhancer mutation which alters 3D genome conformation, impairing recruitment of the transcriptional repressor EHMT2/G9a/KMT1C, thereby alleviating transcriptional repression of ESR1 in EC. Conclusions: In summary, we identify a complex genomic-epigenomic interplay in EC development and progression, altering 3D genome organization to enhance expression of the critical driver ERα.</p

Cochlear Implant Outcomes: A Focused Way of Looking at Speech Perception and Health-Related Quality of Life.

INTRODUCTION: The relationship between health-related quality of life (HRQoL) and speech perception in cochlear implant (CI) users is inconsistent across existing research. To investigate this relationship, we assessed HRQoL using the Glasgow Benefit Inventory (GBI) and speech perception using the Minimum Speech Test Battery (MSTB). The present study proposes an additional subscore to the GBI: CI global outcomes. METHODS: Seventeen bimodal CI users between the ages of 55 and 85 years participated in the study. All participants completed the GBI as well as the MSTB (e.g., AzBio sentence test in quiet and noise, the Bamford-Kowal-Bench Speech-in-Noise test [BKB-SIN], and the Consonant-Nucleus-Consonant test [CNC]). Correlations were calculated between HRQoL and speech perception measures. RESULTS: Improvement in QoL as measured by the GBI CI global outcomes subscore significantly related to better performance on the AzBio in noise. No other significant relationships between the GBI and CI speech perception ability were observed. CONCLUSION: CI global outcomes significantly related to speech perception ability in noise (AzBio), suggesting that this novel metric may be useful for capturing bimodal CI patient-reported outcomes

Improving Clinical Care for Cochlear Implant Recipients: The Coupling of Health-Related-Quality-of-Life and Clinical Speech Measures

https://digitalcommons.providence.org/swedish_fish_2025/1004/thumbnail.jp