Mayo Clinic Laboratory and Pathology Research Roundup: May 15

By Kelley Luedke • May 15, 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

Androgen Receptor Variant AR-V9 is Co-Expressed with AR-V7 in Prostate Cancer Metastases and Predicts Abiraterone Resistance

Androgen receptor (AR) variant AR-V7 is a ligand-independent transcription factor that promotes prostate cancer resistance to AR-targeted therapies. Accordingly, efforts are underway to develop strategies for monitoring and inhibiting AR-V7 in castration-resistant prostate cancer (CRPC). The purpose of this study was to understand whether other AR variants may be co-expressed with AR-V7 and promote resistance to AR-targeted therapies. Mayo Clinic researchers utilized complementary short- and long-read sequencing of intact AR mRNA isoforms to characterize AR expression in CRPC models. Co-expression of AR-V7 and AR-V9 mRNA in CRPC metastases and circulating tumor cells was assessed by RNA-seq and RT-PCR, respectively. Expression of AR-V9 protein in CRPC models was evaluated with polyclonal antisera. Multivariate analysis was performed to test whether AR variant mRNA expression in metastatic tissues was associated with a 12-week progression-free survival endpoint in a prospective clinical trial of 78 CRPC-stage patients initiating therapy with the androgen synthesis inhibitor, abiraterone acetate. The results found that AR-V9 was frequently co-expressed with AR-V7. Both AR variant species were found to share a common 3' terminal cryptic exon, which rendered AR-V9 susceptible to experimental manipulations that were previously-thought to target AR-V7 uniquely. AR-V9 promoted ligand-independent growth of prostate cancer cells. High AR-V9 mRNA expression in CRPC metastases was predictive of primary resistance to abiraterone acetate (HR = 4.0, 95% CI = 1.31-12.2, P = 0.02). In conclusion, AR-V9 may be an important component of therapeutic resistance in CRPC. The study was published in Clinical Cancer Research.

Published to PubMed This Week

• INDIE-HFpEF (Inorganic Nitrite Delivery to Improve Exercise Capacity in Heart Failure With Preserved Ejection Fraction): Rationale and Design
  Circulation: Heart Failure
• Serial Measurements of Circulating Plasma Cells Before and After Induction Therapy Has an Independent Prognostic Impact in Patients with Multiple Myeloma Undergoing Upfront Autologous Transplantation
  Haematologica
  
• Mantle Cell Involvement of the Spleen
  Mayo Clinic Proceedings
• Clinical Spectrum and Clonal Evolution in Germline Syndromes with Predisposition to Myeloid Neoplasms
  British Journal of Haematology
• North Central Cancer Treatment Group N0543 (Alliance): A Phase 2 Trial of Pharmacogenetic-Based Dosing of Irinotecan, Oxaliplatin, and Capecitabine as First-Line Therapy for Patients with Advanced Small Bowel Adenocarcinoma
  Cancer
• Multivariate Model to Identify Women at Low Risk of Cancer Upgrade After a Core Needle Biopsy Diagnosis of Atypical Ductal Hyperplasia
  Breast Cancer Research and Treatment
• A Phase I Study of Cilengitide and Paclitaxel in Patients with Advanced Solid Tumors
  Cancer Chemotherapy Pharmacology
• Medical Cannabis Use Among Patients with Chronic Pain in an Interdisciplinary Pain Rehabilitation Program: Characterization and Treatment Outcomes
  Journal of Substance Abuse Treatment
• Abnormal Uterine Bleeding Is Associated With Increased BMP7 Expression in Human Endometrium
  Reproductive Sciences
• Laboratory Testing for Monoclonal Gammopathies: Focus on Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma
  Clinical Biochemistry
• Helcococcus kunzii Prosthetic Valve Endocarditis Secondary to Lower Extremity Cellulitis
  BMJ Case Reports
• Novel de Novo Variant in EBF3 is Likely to Impact DNA Binding in a Patient with a Neurodevelopmental Disorder and Expanded Phenotypes: Patient Report, in silico Functional Assessment, and Review of Published Cases
  Cold Spring Harbor Molecular Case Studies
• What to Do When You Question Cardiac Troponin Values
  European Heart Journal: Acute Cardiovascular Care

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.