Mayo Clinic Laboratory and Pathology Research Roundup: Aug. 21

By Kelley Luedke • August 21, 2017

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The Research Roundup provides an overview of the past week’s research from Mayo Medical Laboratories consultants, including featured abstracts and complete list of published studies and reviews.

Featured Abstract

Intrinsic BET Inhibitor Resistance in SPOP-Mutated Prostate Cancer Is Mediated by BET Protein Stabilization and AKT-mTORC1 Activation

Bromodomain and extraterminal domain (BET) protein inhibitors are emerging as promising anticancer therapies. The gene encoding the E3 ubiquitin ligase substrate-binding adaptor speckle-type POZ protein (SPOP) is the most frequently mutated in primary prostate cancer. Mayo Clinic researchers demonstrated that wild-type SPOP binds to and induces ubiquitination and proteasomal degradation of BET proteins (BRD2, BRD3 and BRD4) by recognizing a degron motif common among them. In contrast, prostate cancer-associated SPOP mutants show impaired binding to BET proteins, resulting in decreased proteasomal degradation and accumulation of these proteins in prostate cancer cell lines and patient specimens and causing resistance to BET inhibitors. Transcriptome and BRD4 cistrome analyses reveal enhanced expression of the GTPase RAC1 and cholesterol-biosynthesis-associated genes together with activation of AKT-mTORC1 signaling as a consequence of BRD4 stabilization. This data show that resistance to BET inhibitors in SPOP-mutant prostate cancer can be overcome by combination with AKT inhibitors and further support the evaluation of SPOP mutations as biomarkers to guide BET-inhibitor-oriented therapy in patients with prostate cancer. The study was published in Nature Medicine.

Published to PubMed This Week

• Eliminating Creatine Kinase-Myocardial Band Testing in Suspected Acute Coronary Syndrome: A Value-Based Quality Improvement
  JAMA Internal Medicine
• Accuracy and Safety of the Cytosponge for Assessing Histologic Activity in Eosinophilic Esophagitis: A Two-Center Study
  American Journal of Gastroenterology
  
• Constipation-Predominant Irritable Bowel Syndrome Females Have Normal Colonic Barrier and Secretory Function
  American Journal of Gastroenterology
• Open-Capsule Budesonide for Refractory Celiac Disease
  American Journal of Gastroenterology
• Predictors of Progression in Barrett's Esophagus with Low-Grade Dysplasia: Results from a Multicenter Prospective BE Registry
  American Journal of Gastroenterology
• High-Resolution, Accurate-Mass (HRAM) Mass Spectrometry Urine Steroid Profiling in the Diagnosis of Adrenal Disorders
  Clinical Chemistry
• Predictive Models in the Diagnosis and Treatment of Autoimmune Epilepsy
  Epilepsia
• Characteristics and Long-Term Outcomes of Head and Neck Squamous Cell Carcinoma After Solid Organ Transplantation
  Oral Oncology
• Laboratory Diagnostics for Fungal Infections: A Review of Current and Future Diagnostic Assays
  Clinics in Chest Medicine
• NanoString-Based Breast Cancer Risk Prediction for Women with Sclerosing Adenosis
  Breast Cancer Research and Treatment
• External Validation of a 5-Year Survival Prediction Model After Elective Abdominal Aortic Aneurysm Repair
  Journal of Vascular Surgery
• A Longitudinal Study of Whole Body, Tissue, and Cellular Physiology in a Mouse Model of Fibrosing NASH With High Fidelity to the Human Condition
  American Journal of Physiology-Gastrointestinal and Liver Physiology
• Gene-Panel Testing of Breast and Ovarian Cancer Patients Identifies a Recurrent RAD51C Duplication
  Clinical Genetics
• Evaluation of the CLSI EP26-A Protocol for Detection of Reagent Lot-to-Lot Differences
  Clinical Biochemistry
• Fibrohistiocytic Tumors
  Clinics in Laboratory Medicine
• Conditions Simulating Primary Bone Neoplasms
  Surgical Pathology Clinics
• Combining a Nontargeted and Targeted Metabolomics Approach to Identify Metabolic Pathways Significantly Altered in Polycystic Ovary Syndrome
  Metabolism

Kelley Luedke

Kelley Luedke is a Marketing Channel Manager at Mayo Clinic Laboratories. She is the principle editor and writer of Insights and leads social media and direct marketing strategy. Kelley has worked at Mayo Clinic since 2013. Outside of work, you can find Kelley running, traveling, playing with her kitty, and exploring new foods.