WIP 41 - Identifying and Reclassifying Variants of Unknown Significance Associated with Cancer Predisposition Syndromes in a Bronx Pediatric Oncology Population
Resident The Children's Hospital at Montefiore New York, New York, United States
Background: Genetic testing in pediatric oncology can uncover rare genetic predisposition syndromes that magnify the risk of future cancer development. Little is understood about causation, treatment, and optimal surveillance of these syndromes. Genetic testing routinely performed in our Childhood Cancer Predisposition (CCP) Clinic may reveal benign or pathogenic results, or variants of uncertain significance (VUS). Patients carrying VUS are not offered the enhanced management or testing available to those with positive genetic findings. Genetic testing in non-white populations typically reveals higher incidence of VUS due to underrepresentation in national genomic databases. We hypothesize that pathogenic variants in cancer predisposition genes are underreported in the highly diverse Bronx pediatric oncology population and aim to reclassify VUS as pathogenic or benign and analyze their potential associations with disease. Objective: Calculate the spectrum/frequency of VUS in patients seen at the CCP clinic and reclassify VUS in this population as pathogenic or benign. Design/Methods: We are screening all pediatric oncology patients managed over the past 10 years at our institution for risk of carrying cancer predisposition syndromes. At-risk patients will be offered genetic testing through the CCP clinic and enrollment into an IRB-approved, HIPAA-compliant database compiling relevant genetic and clinical information summarized by standard descriptive statistics. Patient recruitment into the database will occur from 12/23-3/24. We will use this database to define the frequency and spectrum of genetic variants and measure VUS prevalence in this population. Patients with VUS will be assessed by CCP staff for possible variant reclassification and supportive data will be communicated to CLIA certified genetic testing labs to attempt reclassification. Data analysis will occur from 3/24-4/24.
