Mayo Clinic laboratory and pathology research roundup: April 13
The research roundup provides an overview of the past week’s research from Mayo Clinic Laboratories consultants, including featured abstracts and a complete list of published studies and reviews.
Resistance to next-generation anti-androgen enzalutamide (ENZ) constitutes a major challenge for the treatment of castration-resistant prostate cancer (CRPC). By performing genome-wide ChIP-seq profiling in ENZ-resistant CRPC cells we identify a set of androgen receptor (AR) binding sites with increased AR binding intensity (ARBS-gained). While ARBS-gained loci lack the canonical androgen response elements (ARE) and pioneer factor FOXA1 binding motifs, they are highly enriched with CpG islands and the binding sites of unmethylated CpG dinucleotide-binding protein CXXC5 and the partner TET2. RNA-seq analysis reveals that both CXXC5 and its regulated genes including ID1 are upregulated in ENZ-resistant cell lines and these results are further confirmed in patient-derived xenografts (PDXs) and patient specimens. Consistent with the finding that ARBS-gained loci are highly enriched with H3K27ac modification, ENZ-resistant PCa cells, organoids, xenografts and PDXs are hyper-sensitive to NEO2734, a dual inhibitor of BET and CBP/p300 proteins. These results not only reveal a noncanonical AR function in acquisition of ENZ resistance, but also posit a treatment strategy to target this vulnerability in ENZ-resistant CRPC. Via Nature communications.
Published to PubMed This Week
- Juvenile papillomatosis of breast.
Mayo Clinic Proceedings
- Genetic predictors of chemotherapy-induced peripheral neuropathy from paclitaxel, carboplatin and oxaliplatin: NCCTG/Alliance N08C1, N08CA and N08CB study.
- Fatty acid synthase confers tamoxifen resistance to ER+/HER2+ breast cancer.
- Stem cell therapy for microvascular injury associated with ischemic nephropathy.
- Anesthesiology residents' experiences and perspectives of residency training.
Anesthesiology and Analgesia
- Automated identification of glomeruli and synchronized review of special stains in renal biopsies by machine learning and slide registration: A cross-institutional study.
- Metastatic or suspected metastatic cancer in patients 90 years of age or older: A single-institution, multi-site study.
Journal of Geriatric Oncology
- Dosimetric assessment of a high precision system for mouse proton irradiation to assess spinal cord toxicity.
- Assessment of isochromosome 12p & 12p abnormalities in germ cell tumors using FISH, SNP-Arrays & NGS/ Mate-Pair sequencing.
- What to do when the gold standard isn't accessible?