Molecular and immune landscape of early-onset versus average-onset well-differentiated enteropancreatic neuroendocrine tumors.

643 Background: The incidence of neuroendocrine tumors (NETs) has increased over the past few decades, especially among younger patients. While data from other gastrointestinal malignancies suggest early-onset may be associated with biological differences, this is yet to be investigated in NETs. We sought to characterize the molecular and immune landscape of early (EO)- versus average-onset (AO) pancreatic (pNETs) and small intestinal NETs (siNETs). Methods: Cases with metastatic pNETs and siNETs sequenced using the Tempus xT assay were included. DNA sequencing was performed to identify somatic alterations and whole transcriptome RNA-seq data were normalized to log2(TPM+1) with assay correction. Immune profiling analysis included tumor mutational burden (TMB), microsatellite instability (MSI), PD-L1 status, and immune infiltration estimated via quanTIseq. Differential expression between EO (50 years) was assessed using Wilcoxon rank sum tests with Benjamini–Hochberg correction, and pathway enrichment was assessed via GSEA (Gene Set Enrichment Analysis). Statistical significance was defined as p