FY25 Project Inherited Cancer Risk

ABSTRACT “Project Inherited Cancer Risk” is an observational, non-randomized study evaluating the integration of precision personalized medical treatment based on clinically relevant germline mutations and polymorphisms in pediatric or adolescent and young adult (AYA) patients receiving primary oncology care in the DanceBlue Pediatric Hematology/Oncology Clinic at the University of Kentucky. Newly diagnosed patients through 29 years of age with cancer will be recruited onto this study. Exome sequencing will be done on the patient’s non-malignant tissue (blood or skin sample) and evaluated for mutations in germline cancer-predisposition genes , pharmacogenomic genes pertinent to drug and medication effects, and actionable genes that the Americ an College of Medical Genetics and Genomics (ACMG) has recommended for reporting during exome sequencing. Pediatric oncology data will be incorporated into the Markey Cancer Center’s Cancer Data Commons databas e and combined for informatics analysis. A blood or skin sample will be collected, sent for DNA testing and bio- banking in the Markey Cancer Center’s Biospecimen and Tissue Procurement Shared Resource Facility, and a report will be generated identifying mutations in the targeted gene panels tested. We will develop a multidisciplinary UK Healthcare Pediatric Oncology Precision Medicine Team composed of clinical providers , experts in NextGen sequencing, bioinformaticians, pathologists, nurses, pharmacists, pharmacologists, genetic counselors, statisticians and research staff. This group will meet monthly to review patient sequencing reports in the context of a Pediatric Germline Molecular Tumor Board and make recommendations by generating a consultation report that will be added to the patient’s electronic medical record. Patients with identified germline cancer predisposition syndromes will be referred to the UK Pediatric, Adolescent and Young Adult Cancer Predisposition Service for further evaluation and management by a cancer genetic counselor and pediatric oncologist, and families of identified patients will be referred to Cancer Genetics at the Markey Cancer Center for consultation and testing as needed. All patients and families involved in the study will be educated about their risk for hereditary cancer. If pharmacogenomic variants are identified, that information will be provided to the pediatric oncology pharmacy team to be considered for medication dosing and toxicity, as well as provided to the patient’s other care providers. If actionable mutations in the ACMG gene panel are identified, the patient will be referred to General Genetics for further counseling and management. It is our intention to maximiz e quality of life and long-term outcome by identifying cancer predisposition syndromes as early as possible.