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

Abstract

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.