Mayo Clinic laboratory and pathology research roundup: March 30

By Samantha Rossi • March 30, 2021

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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.

Featured Abstract

A noncanonical AR addiction drives enzalutamide resistance in prostate cancer.

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.

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Published to PubMed This Week

• Utility of mismatch repair protein expression screening via an endoscopic ultrasound assessment of treatment-naive pancreas ductal adenocarcinoma.
  Gut
• Myeloid bodies in acute tubular injury.
  Kidney International
• Characteristics and outcomes of therapy-related myeloid neoplasms following autologous stem cell transplantation for multiple myeloma.
  Blood Cancer Journal
• Outcomes on anti-VEGFR-2/paclitaxel treatment following progression on immune checkpoint inhibition in patients with metastatic gastroesophageal adenocarcinoma.
  International Journal of Cancer
• Recurrent novel HMGA2-NCOR2 fusions characterize a subset of keratin-positive giant cell-rich soft tissue tumors.
  Modern Pathology
• Inflammatory rhabdomyoblastic tumor with progression to high-grade rhabdomyosarcoma.
  Modern Pathology
• Loss of putative GABAergic neurons in the ventrolateral medulla in multiple system atrophy.
  Sleep
• The prognostic significance of del6q23 in chronic lymphocytic leukemia.
  American Journal of Hematology
• Alterations of mesenchymal stromal cells in cerebrospinal fluid: insights from transcriptomics and an ALS clinical trial.
  Stem Cell Research Therapy
• Phenotypic and genomic profiling of Staphylococcus argenteus in Canada and the United States and recommendations for clinical result reporting.
  Journal of Clinical Microbiology

Samantha Rossi

Samantha Rossi is a Digital Marketing Manager at Mayo Clinic Laboratories. She supports marketing strategies for product management and specialty testing. Samantha has worked at Mayo Clinic since 2019.