Comparative analysis of potentially actionable genomic alterations in early-onset versus later-onset gastrointestinal cancers.

846 Background: There is an alarming rise in early-onset (EO) gastrointestinal (GI) cancers, which may have distinct genomic profiles compared with later-onset (LO) cases. OncoKB is a validated database that provides evidence-based annotation of genomic alterations with therapeutic relevance. Utilizing the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) v18.0 and OncoKB annotator, we performed a comprehensive analysis of OncoKB-actionable alterations across all GI tumors. Methods: The AACR GENIE v18.0 database was used to select GI cancers samples by OncoTree code, which were classified by tumor group. We utilized OncoKB to annotate all samples and their somatic mutations, copy number alterations, and structural variants by therapeutic level of evidence (Levels 1-4). We considered a tumor sample to have a potentially actionable alteration if there was at least one Level 1-3B alteration present. We defined EO as age < 50 and LO as age ≥ 50, and excluded samples without age. Chi-square testing compared frequency of actionable alterations between EO and LO tumor groups, and Benjamini-Hochberg procedure controlled for false discovery rate (statistical significance for q