117. Clinical lessons learned from Translational Molecular Profiling of Cancer and Somatic Disease

Aly Abdelkareem

Kathleen Schieffer

Kathleen M. Schieffer, PhD, FACMG, is a clinical laboratory director within the Institute for Genomic Medicine at Nationwide Children’s Hospital and an Assistant Professor – Clinical within the Department of Pathology at the Ohio State University College of Medicine. She received a dual-title PhD in Biomedical Sciences and Clinical and Translational Science at the Pennsylvania State University College of Medicine, where she studied the transcriptome and microbiome of colonic tissue from individuals with diverticulitis. Her postdoctoral work with the Institute for Genomic Medicine at Nationwide Children’s Hospital focused on genomic and transcriptomic analysis in patients with rare and refractory hematologic disease, cancer, and somatic disease enrolled on our institutional translational cancer genomics protocol. She completed a Laboratory Genetics and Genomics fellowship at Nationwide Children’s Hospital in 2021. Her current interests focus on the use of cytogenetic and molecular assays to better characterize germline and somatic disease.


Kathleen Schieffer, Mariam Mathew, Kristy Lee, Samantha Choi, Elizabeth Varga, Emma Garval, Olivia Grischow, Aimee Jalkanen, Vijayakumar Jayaraman, Don Corsmeier, Ben Kelly, Peter Chang, James Fitch, Katherine Miller, Daniel Koboldt, Peter White, Vincent Magrini, Richard Wilson, Elaine Mardis, Catherine Cottrell

Nationwide Children’s Hospital, Columbus, OH, USA

Our pediatric, tertiary care institution developed a translational protocol to evaluate the genomic landscape of hematologic disease, solid tumors, and somatic disease among pediatric and adolescent patients. We aim to provide results that refine diagnosis, identify targeted therapeutics, determine eligibility for clinical trials, inform prognosis, and identify germline cancer predisposition. Translational research findings are discussed at multidisciplinary conferences, involving clinicians, pathologists, surgeons, radiologists, radiation oncologists, and genomic medicine. Findings that may impact patient care are confirmed in our CAP-accredited, CLIA-certified clinical lab and reported in the patient medical record. Over four years, 448 patients were nominated onto this protocol, 380 (85%) consented, and 346 (77%) sequenced using paired disease-involved/germline comparator exome sequencing and RNA-sequencing. DNA-based methylation was performed on a subset of solid tumor cases (n=188). Germline findings were identified in 99 (22%) patients, including 9 with Li-Fraumeni syndrome, 6 with neurofibromatosis type 1 (NF1), 5 with rhabdoid tumor predisposition syndrome (RTPS), and 3 with Noonan syndrome. Notably, a diagnosis was established from this translational testing with follow up clinical confirmation and appropriate genetic counseling for 11 (2.5%) individuals (Li-Fraumeni syndrome n=5, Lynch syndrome n=2, schwannomatosis n=2, Noonan syndrome n=2, RTPS n=1, NF1 n=1). Outcome data was captured on 251 (56%) individuals thus far, with refinement/reclassification of diagnosis for 82 (33%) individuals, refinement of treatment for 32 (13%) individuals, and refined prognostication for 66 (26%) individuals. Through multidisciplinary collaboration with a team of clinician colleagues, we demonstrated clinical utility in identifying germline disease and characterization of medically meaningful somatic findings.