PATH-58. SEQUENCING OF DNA RECOVERED FROM BRAIN TUMOR BIOPSY SURGICAL WASTE IMPROVES SENSITIVITY OF RAPID IDH/TP53-MUTANT TUMOR DIAGNOSES

Abstract BACKGROUND TP53 and IDH mutations are common in brain tumors and are highly relevant biomarkers for diagnosis and treatment. Thus, biopsy tissue is commonly tested for these mutations via immunohistochemistry (IHC), which is rapid and generally considered highly sensitive. However, IHC only tests for IDH1R132H (80%-90% of IDH mutant disease) and rarer IDH mutations are not covered. p53 nuclear staining is used to identify non-specific p53 upregulation and loss of function but does not test for specific mutations and has a relatively lower overall sensitivity/specificity of ~80%/80-97%. Sequencing can resolve all mutations and improve over IHC, but long turnaround time and high cost prevents this. New advances in rapid sequencing technologies allow same-day, low-cost panel sequencing. However, access to biopsy tissue is zero-sum and obtaining additional tissue for molecular diagnostics confers increased morbidity. We investigate whether tumor DNA recovered from surgical waste (specifically core biopsy needle fluid and non-adherent gauze) is sufficient to diagnose IDH/p53 status of tumors. METHODS Surgeons were instructed to save biopsy needle rinse saline, and/or to recover any non-adherent gauze used in specimen handling. Cell-free DNA was extracted and sequenced using a same-day targeted panel protocol and/or TruSight Oncology 500 panel sequencing. RESULTS 100% of recovered samples yielded enough DNA for targeted sequencing (17/17). In all IDH1R132H IHC positive cases, waste sequencing recapitulated the mutation (4/4). In 7/9 p53 positive cases via IHC (>10% staining), waste sequencing of common hotspot loci was able to identify a specific TP53 mutation. Importantly, sequencing identified alternate IDH mutations in three IHC negative cases (3/13), discovered a rarer TP53 mutation (E286K) in one IHC negative case, and confirmed TP53 negative status in one indeterminate p53 report. CONCLUSIONS Surgical waste is an important diagnostic resource that should be leveraged for rapid diagnostic sequencing. Sufficient DNA can be easily recovered from surgical waste and sequenced within the same time-frame–but with increased sensitivity–to IHC.