Mayo Clinic Laboratory and Pathology Research Roundup: Aug. 6

By Kelley Luedke • August 6, 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

A Novel Enhancer Regulates MGMT Expression and Promotes Temozolomide Resistance in Glioblastoma

Temozolomide (TMZ) was used for the treatment of glioblastoma (GBM) for over a decade, but its treatment benefits are limited by acquired resistance, a process that remains incompletely understood. Mayo Clinic researchers reported that an enhancer, located between the promoters of marker of proliferation Ki67 (MKI67) and O6-methylguanine-DNA-methyltransferase (MGMT) genes, is activated in TMZ-resistant patient-derived xenograft (PDX) lines and recurrent tumor samples. Activation of the enhancer correlates with increased MGMT expression, a major known mechanism for TMZ resistance. The team showed that forced activation of the enhancer in cell lines with low MGMT expression results in elevated MGMT expression. Deletion of this enhancer in cell lines with high MGMT expression leads to a dramatic reduction of MGMT and a lesser extent of Ki67 expression, increased TMZ sensitivity, and impaired proliferation. Together, these studies uncover a mechanism that regulates MGMT expression, confers TMZ resistance, and potentially regulates tumor proliferation. The study was published in Nature Communications.

Published to PubMed This Week

• • • • • DUB3 Promotes BET Inhibitor Resistance and Cancer Progression by Deubiquitinating BRD4
          Molecular Cell
        • Comparison of PD-L1 Immunohistochemical Staining Between EBUS-TBNA and Resected Lung Cancer Specimens
          Chest
        • Myelin Oligodendrocyte Glycoprotein Antibody (MOG-IgG)-Positive Optic Neuritis: Clinical Characteristics, Radiologic Clues and Outcome
          American Journal of Ophthalmology
        • in vitro Activity of Oritavancin in Combination with Rifampin or Gentamicin Against Prosthetic Joint Infection-Associated Methicillin-Resistant Staphylococcus epidermidis Biofilms
          International Journal of Antimicrobial Agents
        • M3RNA Drives Targeted Gene Delivery in Acute Myocardial Infarction
          Tissue Engineering
        • Survival of Staphylococcus Epidermidis in Fibroblasts and Osteoblasts
          Infection and Immunity
        • Endovascular Delivery of Leads and Stentrodes and Their Applications to Deep Brain Stimulation and Neuromodulation: A Review
          Neurosurgical Focus
        • The Utilization of Chromosomal Microarray Technologies for Hematologic Neoplasms: An ACLPS Critical Review
          American Journal of Clinical Pathology
        • Non-Internal Tandem Duplication (ITD), Non-Tyrosine Kinase Domain (TKD) FLT3 Mutations in Myeloid Malignancies: A Brief Report of 10 Patients
          Leukemia Research

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.