Publications by authors named "R R Broaddus"
Article Synopsis
- PAX2 is identified as an endometrial tumor suppressor frequently inactivated through a unique epigenetic mechanism, rather than promoter hypermethylation.
- In 80% of endometrial cancers, the loss of PAX2 is linked to transcriptional silencing, which alters chromatin features, contributing to cancer development.
- The research highlights new pathways for understanding endometrial cancer origins, potentially influencing future diagnosis and treatment approaches.
Missense mutations in exon 3 of , the gene encoding β-catenin, are associated with poor outcomes in endometrial carcinomas (EC). Clinically, mutation status has been difficult to use as a predictive biomarker as β-catenin oncogenic activity is modified by other factors, and these determinants are unknown. Here we reveal that CD73 restrains the oncogenic activity of exon 3 β-catenin mutants, and its loss associates with recurrence.
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- The study aimed to outline how mismatch repair (MMR) and microsatellite instability (MSI) testing is conducted in various laboratories, specifically before the 2022 CAP/AMP guidelines were published.
- Researchers analyzed data from supplementary questionnaires sent to 542 laboratories regarding their testing practices and types of specimens used.
- Results showed that domestic labs test for MSI/MMR more frequently than international ones, with academic hospitals leading in testing rates; most labs are aware of the clinical implications of high MSI or MMR-deficient results for immune checkpoint therapy.
Unlabelled: Lynch syndrome (LS) is defined by inherited mutations in DNA mismatch repair genes, including and carries 60% lifetime risk of developing endometrial cancer (EC). Beyond hypermutability, specific mechanisms for LS-associated endometrial carcinogenesis are not well understood. Here, we assessed the effects of MSH2 loss on EC pathogenesis using a novel mouse model (PR-Cre , abbreviated Msh2KO), primary cell lines established from this model, human tissues, and human EC cell lines with isogenic MSH2 knockdown.
View Article and Find Full Text PDFObjective: MLH1 loss due to methylation, detected during Lynch syndrome screening, is one of the most common molecular changes in endometrial cancer. It is well established that environmental influences such as nutritional state can impact gene methylation, both in the germline and in a tumor. In colorectal cancer and other cancer types, aging is associated with changes in gene methylation.
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