Detection of circulating tumor DNA in patients with osteosarcoma

// David M. Barris 1, * , Shoshana B. Weiner 1, * , Robert A. Dubin 2 , Michael Fremed 1 , Xusheng Zhang 2 , Sajida Piperdi 3 , Wendong Zhang 3 , Shahina Maqbool 1 , Jonathan Gill 4 , Michael Roth 4 , Bang Hoang 5 , David Geller 5 , Richard Gorlick 4 and Daniel A. Weiser 6, 7 1 Department of Genetics and Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA 2 Computational Genomics Core, Albert Einstein College of Medicine, Bronx, NY, USA 3 Department of Pediatrics, Montefiore Medical Center, Bronx, NY, USA 4 Division of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA 5 Department of Orthopedic Surgery, Montefiore Medical Center, Bronx, NY, USA 6 Division of Hematology/Oncology, Children’s Hospital at Montefiore, Bronx, NY, USA 7 Departments of Pediatrics and Genetics, Albert Einstein College of Medicine, Bronx, NY, USA * These authors contributed equally to this work Correspondence to: Shoshana B. Weiner, email: sbweiner@mail.einstein.yu.edu Keywords: circulating tumor DNA; osteosarcoma; targeted sequencing; Next Generation Sequencing; targeted therapy Received: November 28, 2017      Accepted: January 09, 2018      Published: January 18, 2018 ABSTRACT Identification and quantification of somatic alterations in plasma-derived, circulating tumor DNA (ctDNA) is gaining traction as a non-invasive and cost effective method of disease monitoring in cancer patients, particularly to evaluate response to treatment and monitor for disease recurrence. To our knowledge, genetic analysis of ctDNA in osteosarcoma has not yet been studied. To determine whether somatic alterations can be detected in ctDNA and perhaps applied to patient management in this disease, we collected germline, tumor, and serial plasma samples from pediatric, adolescent, and young adult patients with osteosarcoma and used targeted Next Generation Sequencing (NGS) to identify somatic single nucleotide variants (SNV), insertions and deletions (INDELS), and structural variants (SV) in 7 genes commonly mutated in osteosarcoma. We demonstrate that patient-specific somatic alterations identified through comparison of tumor-germline pairs can be detected and quantified in cell-free DNA of osteosarcoma patients.