Mayo Clinic Laboratory and Pathology Research Roundup: Feb. 4

By Kelley Luedke • February 4, 2019

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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

53BP1 as a Potential Predictor of Response in PARP Inhibitor-Treated Homologous Recombination-Deficient Ovarian Cancer

Poly(ADP-ribose) polymerase (PARP) inhibitors have shown substantial activity in homologous recombination- (HR-) deficient ovarian cancer and are undergoing testing in other HR-deficient tumors. For reasons that are incompletely understood, not all patients with HR-deficient cancers respond to these agents. Preclinical studies have demonstrated that changes in alternative DNA repair pathways affect PARP inhibitor (PARPi) sensitivity in ovarian cancer models. This has not previously been assessed in the clinical setting. Clonogenic and plasmid-based HR repair assays were performed to compare BRCA1-mutant COV362 ovarian cancer cells with or without 53BP1 gene deletion. Archival biopsies from ovarian cancer patients in the phase I, open-label clinical trial of PARPi ABT-767 were stained for PARP1, RAD51, 53BP1 and multiple components of the nonhomologous end-joining (NHEJ) DNA repair pathway. Modified histochemistry- (H-) scores were determined for each repair protein in each sample. HRD score was determined from tumor DNA. 53BP1 deletion increased HR in BRCA1-mutant COV362 cells and decreased PARPi sensitivity in vitro. In 36 women with relapsed ovarian cancer, responses to the PARPi ABT-767 were observed exclusively in cancers with HR deficiency. In this subset, 7 of 18 patients had objective responses. The actual HRD score did not further correlate with change from baseline tumor volume. However, in the HR-deficient subset, decreased 53BP1 H-score was associated with decreased antitumor efficacy of ABT-767. The study was published in Gynecologic Oncology.

Published to PubMed This Week

• • • • • Leukemic Transformation among 1306 Patients with Primary Myelofibrosis: Risk Factors and Development of a Predictive Model
          Blood Cancer Journal
          
        • Enhanced Noninvasive Imaging of Oncology Models Using the NIS Reporter Gene and Bioluminescence Imaging
          Cancer Gene Therapy
          
        • Characteristics and Proposed Classification System of Posterior Pilon Fractures
          Medicine
          
        • Imaging Features of Phosphaturic Mesenchymal Tumors
          Skeletal Radiology
          
        • Management of Post-Myocardial Infarction Ventricular Septal Defects: A Critical Assessment
          Journal of Interventional Cardiology
          
        • Comprehensive Characterization of Perioperative Reoperation Following Radical Cystectomy
          Urologic Oncology
          
        • Identification of Aggressive Gardner Syndrome Phenotype Associated with a de novo APC Variant
          Molecular Case Studies

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.