Abstract IA16: Evaluating the implementation and utility of clinical tumor exome sequencing in the pediatric oncology clinic: Early results of the BASIC3 study
Authors: Parsons D. Williams , Roy Angshumoy , Monzon Federico A. , López-Terrada Dolores H. , Chintagumpala Murali M. , Berg Stacey L. , Hilsenbeck Susan G. , Wang Tao , Kerstein Robin A. , Scollon Sarah , Bergstrom Katie , Street Richard L. , McCullough Laurence B. , McGuire Amy L. , Ramamurthy Uma , Wheeler David A. , Eng Christine M. , Yang Yaping , Reid Jeff G. , Muzny Donna M. , Gibbs Richard A. , Plon Sharon E. 
Published: May 2015

Abstract
Advances in sequencing technologies allow for provision of genome-scale data to oncologists and geneticists caring for pediatric cancer patients but current experience with the clinical application of genomic sequencing is limited. The goal of the BASIC3 (Baylor Advancing Sequencing into Childhood Cancer Care) study is to determine the clinical impact of incorporating CLIA-certified tumor and constitutional whole exome sequencing (WES) into the care of children with newly diagnosed solid tumors. This study follows pediatric patients with newly diagnosed CNS and non-CNS solid tumors (target enrollment n=280) at Texas Children's Cancer Center for two years after performing CLIA-certified whole exome sequencing (WES) of blood and frozen tumor samples. Results are deposited into the electronic medical record and disclosed to families by their oncologist and a genetic counselor. The potential impact of tumor exome findings on clinical decision-making is assessed through review of the medical record over the two year follow-up period as well as through surveys of the oncologists regarding prioritization of treatment options in the hypothetical event of tumor recurrence before and after receiving tumor exome results. Preferences of patient families and oncologists for reporting this complex information are obtained by interviews and audiorecording of the exome result disclosure visits. Since the study opened in August 2012, ∼85% of potentially eligible families have consented to enrollment. The first 100 patients comprise a diverse representation of diagnoses, including 32 with CNS tumors (32%) and 68 with non-CNS tumors (68%). Despite limited diagnostic biopsies in many patents, snap-frozen tumor samples adequate for WES were obtained from 84 subjects (84%), including 62/68 non-CNS solid tumors (91%) and 22/32 (69%) CNS solid tumors. Tumor WES results have been reported for the first 55 patients, revealing a median of 9 (range of 0 to 78) protein-altering mutations per tumor and alterations of known cancer genes such as ALK, BRAF, DICER1, KIT, KRAS, NRAS, MET, JAK2, FGFR3, ARID1A, CTNNB1, and TP53. Fourteen of 55 tumors (25%) contained mutations classified as having proven or potential clinical utility. These results demonstrate the feasibility of routine tumor WES in the pediatric oncology clinic and a significant level of parental interest in receiving WES results. Potentially clinically-relevant mutations can be identified in a substantial minority of pediatric solid tumor patients but distinct from the medically actionable mutations seen in adult cancer patients. Data further assessing the clinical utility of the tumor exomes and the preferences of oncologists and parents for reporting of these results are under study. Supported by NHGRI/NCI 1U01HG006485.
Citation Format: D. Williams Parsons, Angshumoy Roy, Federico A. Monzon, Dolores H. López-Terrada, Murali M. Chintagumpala, Stacey L. Berg, Susan G. Hilsenbeck, Tao Wang, Robin A. Kerstein, Sarah Scollon, Katie Bergstrom, Richard L. Street, Jr., Laurence B. McCullough, Amy L. McGuire, Uma Ramamurthy, David A. Wheeler, Christine M. Eng, Yaping Yang, Jeff G. Reid, Donna M. Muzny, Richard A. Gibbs, Sharon E. Plon. Evaluating the implementation and utility of clinical tumor exome sequencing in the pediatric oncology clinic: Early results of the BASIC3 study. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr IA16.