Abstract IA16: Clinical genomics for children with solid tumors: Current realities and future opportunities
Authors: Parsons D. William , Roy Angshumoy , Yang Yaping , Wang Tao , Scollon Sarah , Bergstrom Katie , Kerstein Robin A. , Gutierrez Stephanie , Bavle Abhishek , Lin Frank Y. , López-Terrada Dolores H. , Monzon Federico A. , Nuchtern Jed G. , Ramamurthy Uma , McGuire Amy L. , Hilsenbeck Susan G. , Reid Jeffrey G. , Muzny Donna M. , Wheeler David A. , Berg Stacey L. , Chintagumpala Murali M. , Eng Christine M. , Gibbs Richard A. , Plon Sharon E. 
Published: May 2016

Genome-scale sequencing methods such as whole exome sequencing (WES) have provided significant insight into the pathogenesis of cancer. However, experience with the use of these tests in the clinical care of cancer patients remains limited. Sequencing of tumor and matched normal samples can reveal multiple types of results with implications for clinical practice. The identification of somatic (tumor-specific) mutations has the potential to offer diagnostic and prognostic information and inform selection of therapies. Detection of germline mutations in cancer susceptibility genes may prompt further genetic testing and guide cancer surveillance strategies for both the patient and family members. Germline mutations may also explain non-cancer phenotypes, predict drug responses, or provide reproductive counseling information for parents. The goal of the BASIC3 (Baylor College of Medicine Advancing Sequencing into Childhood Cancer Care) study is to determine the clinical impact of incorporating clinical tumor and constitutional 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 at Texas Children's Cancer Center for two years after performing CLIA-certified WES of blood and frozen tumor samples. Results are deposited into the electronic health 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 audio recording of the WES result disclosure visits. Since the study opened in August 2012, more than 210 subjects have been enrolled (~80% of potentially eligible patients), representing the expected distribution of both CNS and non-CNS tumors. WES results have been reported for 170 subjects, revealing potentially-clinically relevant germline and somatic mutations in cancer genes known to be related to pediatric solid tumors as well as others known to be mutated primarily in adult cancer patients. Data will be presented regarding the diagnostic yield of combined tumor and germline WES for children with newly-diagnosed solid tumors. 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 and have significant implications for the treatment of children with relapsed and refractory solid tumors and the design of clinical trials using precision oncology approaches for these patients. Further analyses of the clinical utility of the WES data and the preferences of oncologists and parents for reporting of these results are under study. The BASIC3 study is a Clinical Sequencing Exploratory Research (CSER) program project supported by NHGRI/NCI 1U01HG006485.

Citation Format: D. William Parsons, Angshumoy Roy, Yaping Yang, Tao Wang, Sarah Scollon, Katie Bergstrom, Robin A. Kerstein, Stephanie Gutierrez, Abhishek Bavle, Frank Y. Lin, Dolores H. López-Terrada, Federico A. Monzon, Jed G. Nuchtern, Uma Ramamurthy, Amy L. McGuire, Susan G. Hilsenbeck, Jeffrey G. Reid, Donna M. Muzny, David A. Wheeler, Stacey L. Berg, Murali M. Chintagumpala, Christine M. Eng, Richard A. Gibbs, Sharon E. Plon. Clinical genomics for children with solid tumors: Current realities and future opportunities. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr IA16.