Mayo Clinic Laboratory and Pathology Research Roundup: Jan. 15

By Kelley Luedke • January 15, 2018

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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

Loss of FOXO1 Cooperates with TMPRSS2-ERG Overexpression to Promote Prostate Tumorigenesis and Cell Invasion

E26 transformation-specific transcription factor ERG is aberrantly overexpressed in approximately 50% of all human prostate cancer due to TMPRSS2-ERG gene rearrangements. However, mice with prostate-specific transgenic expression of prostate cancer-associated ERG alone fail to develop prostate cancer, highlighting that ERG requires other lesions to drive prostate tumorigenesis. Forkhead box (FOXO) transcription factor FOXO1 is a tumor suppressor that is frequently inactivated in human prostate cancer. Mayo Clinic researchers demonstrate that FOXO1, but not other FOXO proteins (FOXO3 and FOXO4), binds and inhibits the transcriptional activity of prostate cancer-associated ERG independently of FOXO1 transcriptional activity. Knockdown of endogenous FOXO1 increased invasion of TMPRSS2-ERG fusion-positive VCaP cells, an effect completely abolished by ERG knockdown. Patient specimen analysis demonstrated that FOXO1 and ERG protein expression inversely correlated in a subset of human prostate cancer. Although human ERG transgene expression or homozygous deletion of Foxo1 alone in the mouse prostate failed to promote tumorigenesis, concomitant ERG transgene expression and Foxo1 deletion resulted in upregulation of ERG target genes, increased cell proliferation, and formation of high-grade prostatic intraepithelial neoplasia. Overall, they provide biochemical and genetic evidence that aberrantly activated ERG cooperates with FOXO1 deficiency to promote prostate tumorigenesis and cell invasion. The findings enhance understanding of prostate cancer etiology and suggest that the FOXO1-ERG signaling axis can be a potential target for treatment of prostate cancer. The study was published in Cancer Research.

Published to PubMed This Week

• • Features of Adult Autoimmune Enteropathy Compared With Refractory Celiac Disease
    Clinical Gastroenterology and Hepatology
  • EUS Fine Needle Biopsy Can Determine PD-L1 Immune Biomarker Status in Treatment Naïve Pancreatic Ductal Adenocarcinoma
    Clinical Gastroenterology and Hepatology
  • Direct-to-Consumer Testing 2.0: Emerging Models of Direct-to-Consumer Genetic Testing
    Mayo Clinic Proceedings
  • Progressive Multifocal Leukoencephalopathy
    Mayo Clinic Proceedings
  • Bulbar Conjunctival Nodule in a Patient With Rheumatoid Arthritis
    JAMA Ophthalmology
  • Beta-Defensin 1, Aryl Hydrocarbon Receptor and Plasma Kynurenine in Major Depressive Disorder: Metabolomics-Informed Genomics
    Translational Psychiatry
  • Cytotechnologists as Coinvestigators in Anatomical Pathology Research
    Cancer
  • Phase 1/2 Trial of Temsirolimus and Sorafenib in the Treatment of Patients with Recurrent Glioblastoma: North Central Cancer Treatment Group Study/Alliance N0572
    Cancer
  • Histologic and Immunohistochemical Differences Between Hereditary and Sporadic Diffuse Gastric Carcinoma
    Human Pathology
  • Up-and-Over Technique for Implantation of Iliac Branch Devices After Prior Aortic Endograft Repair
    Journal of Endovascular Therapy
  • Preliminary Results of Tissue-Engineered Injection Laryngoplasty Material in a Rabbit Model
    Laryngoscope
  • Comparing Analytical Outliers and the Percent of Emergency Department Patients with Results Above the 99th Percentile Upper Reference Limit for 2 Conventional and One High Sensitivity Troponin Assay
    Clinical Biochemistry
  • Myeloid Neoplasm with Eosinophilia Associated with Isolated Extramedullary FIP1L1/PDGFRA Rearrangement
    Cancer Genetics
  • De novo Donor Specific Antibody following BK Nephropathy: The Incidence and Association with Antibody Mediated Rejection
    Clinical Transplantation
  • Low-Grade Fibromyxoid Sarcoma Arising Within the Median Nerve
    Neuropathology

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.