The goal of this Exploratory Clinical Sequencing project is to integrate CLIA-certified germ line and tumor exome sequencing information generated by the Whole Genome Laboratory into the care of childhood cancer patients with high-risk solid tumors and brain tumors at the Texas Children's Cancer Center. Given the clinical nature of the project the dual principal investigators will be Drs. Donald W. Parsons and Sharon E. Plon, board-certified pediatric oncologist and medical geneticist, respectively. We will assess the impact of whole exome sequence data reported by a novel web-based platform with links to existing data for each variant reported and presented through a graphical display that will facilitate physician disclosure of complex data to parents. We will evaluate physician-parent communication and clinical decision-making in the context of two clinical questions (1) How does the availability of tumor whole exome sequence data affect physician recommendations regarding enrollment on specific clinical trials and the treatment plans chosen in the scenario of tumor recurrence? (2) How does the availability of germline whole exome sequence data affect cancer surveillance for patients and genetic testing and cancer surveillance for family members? Quantitative analysis of physician communication in disclosure of genome-scale data will be performed. Parental understanding and preferences for receiving genome scale data will be assessed. Ethical issues related to the appropriate use and reporting of whole exome data including possible incidental findings in a pediatric setting will be addressed. Baylor College of Medicine is ideally suited to conduct this study with the longstanding clinical oncology and cancer genetics practices, extensive expertise in genomics through the Human Genome Sequencing Center, the largest academic CLIA-certified molecular diagnostic laboratory in the United States and a track record of scholarship in ethical and social implications of genomics in the Center for Medical Ethics and Health Policy and physician-patient/parent communication in the Division of Health Outcome Services.

Public Health Relevance

The recent deluge of genetic data has translated into an exponential increase in the number of 'molecularly targeted' pediatric cancer clinical trials. Therefore, an investigation of the impact of genomic sequence data on decision making of physicians and parents in relation to cancer risk and selection of treatment at the time of tumor recurrence would have significant impact and relevance for the field of pediatric oncology.

National Institute of Health (NIH)
National Human Genome Research Institute (NHGRI)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel ()
Program Officer
Hindorff, Lucia
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Baylor College of Medicine
Schools of Medicine
United States
Zip Code
Posey, Jennifer E; Harel, Tamar; Liu, Pengfei et al. (2017) Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation. N Engl J Med 376:21-31
Wolf, Susan M; Amendola, Laura M; Berg, Jonathan S et al. (2017) Navigating the research-clinical interface in genomic medicine: analysis from the CSER Consortium. Genet Med :
Brodeur, Garrett M; Nichols, Kim E; Plon, Sharon E et al. (2017) Pediatric Cancer Predisposition and Surveillance: An Overview, and a Tribute to Alfred G. Knudson Jr. Clin Cancer Res 23:e1-e5
O'Daniel, Julianne M; McLaughlin, Heather M; Amendola, Laura M et al. (2017) A survey of current practices for genomic sequencing test interpretation and reporting processes in US laboratories. Genet Med 19:575-582
Stankiewicz, Pawe?; Khan, Tahir N; Szafranski, Przemyslaw et al. (2017) Haploinsufficiency of the Chromatin Remodeler BPTF Causes Syndromic Developmental and Speech Delay, Postnatal Microcephaly, and Dysmorphic Features. Am J Hum Genet 101:503-515
Potter, Samara L; Venkatramani, Rajkumar; Wenderfer, Scott et al. (2017) Renal cell carcinoma harboring somatic TSC2 mutations in a child with methylmalonic acidemia. Pediatr Blood Cancer 64:
Mody, Rajen J; Prensner, John R; Everett, Jessica et al. (2017) Precision medicine in pediatric oncology: Lessons learned and next steps. Pediatr Blood Cancer 64:
Amendola, Laura M; Jarvik, Gail P; Leo, Michael C et al. (2016) Performance of ACMG-AMP Variant-Interpretation Guidelines among Nine Laboratories in the Clinical Sequencing Exploratory Research Consortium. Am J Hum Genet 99:247
Brothers, Kyle B; Holm, Ingrid A; Childerhose, Janet E et al. (2016) When Participants in Genomic Research Grow Up: Contact and Consent at the Age of Majority. J Pediatr 168:226-31.e1
Bissig-Choisat, Beatrice; Kettlun-Leyton, Claudia; Legras, Xavier D et al. (2016) Novel patient-derived xenograft and cell line models for therapeutic testing of pediatric liver cancer. J Hepatol 65:325-33

Showing the most recent 10 out of 45 publications