Performance Of Genomic Data Strategies For Cancer Precision Medicine Across Distinct Contexts And Ethnicities.

1500Background: The expanding appeal of clinical tumor profiling has led to many sequencing strategies, ranging from small gene panels to exomes, with or without patient-matched germline data. This diversity of approaches may engender uncertainty about their benefits and liabilities, particularly in light of reported germline false positives in tumor-only profiling, and emerging immunotherapies that leverage genome-wide data. Methods: We modeled common tumor profiling modalities - large (n = 300 genes) and small (n= 15 or 48 genes) panels - onto clinical whole exomes (WES) from 157 patients with lung or colon adenocarcinoma. We created a tumor-only analysis algorithm to assess germline false positives (variants erroneously called as somatic), impact of patient ethnicity on results, and neoantigen detection. Results: The germline false positive rate with tumor-only large panel sequencing was 14% (144/1012 variants). For patients whose results underwent molecular pathologist review, 50/54 (93%) false positi...